1. NCCU Academic Hub
  2. 學術產出
  3. College of Science
  4. Theses
  5. Item

學術產出-Theses

Article View/Open

Publication Export

Google ScholarTM

政大圖書館

Citation Infomation

  • No doi shows Citation Infomation
題名 漢厚朴酚與蛋白激酶 CK2 的交互作用對 Nrf1 蛋白調控蛋 白酶體活性的影響
The interactive effects of honokiol and protein kinase CK2α on the Nrf1-mediated proteasome activity
作者 吳芊澐
貢獻者 趙知章
Chao, Chih Chang
吳芊澐
關鍵詞 漢厚朴酚
蛋白激酶 CK2
Nrf1 蛋白
抗細胞凋亡Mcl -1蛋白
蛋白酶體活性
Honokiol
protein kinase CK2
Nrf1
Mcl-1
proteasome activity
日期 2013
上傳時間 1-Sep-2014 13:48:34 (UTC+8)
摘要 漢厚朴酚是從木蘭科植物中萃取之天然化合物，已知具有抗氧化、抗發炎及神經保護之生理活性功能。先前的研究證明漢厚朴酚可以保護多巴胺神經元對抗6-OHDA所引起的細胞傷害，並且可以減緩6-OHDA 動物模式由apomorphine所誘發的旋轉行為，但漢厚朴酚對於神經保護之分子機制的相關研究尚未釐清。蛋白激酶CK2是具有多功能的絲氨酸/蘇氨酸激酶，高度表現在大腦紋狀體中，先前的研究證實蛋白激酶CK2參與調節神經系統功能和具有神經保護之作用。先前研究也指出轉錄因子Nrf1（Nuclear factor E2-related factor 1）是蛋白激酶CK2下游磷酸化受質，會調控小鼠胚胎纖維細胞中蛋白酶體基因的表現。抗細胞凋亡蛋白Mcl-1 (myeloid cell leukemia 1) 屬於Bcl-2蛋白家族的成員之一，在細胞凋亡的過程中，其蛋白含量減少與細胞凋亡有密切關聯性，抑制Mcl-1蛋白的降解可以延遲細胞死亡。因此本論文主要探討漢厚朴酚的神經細胞保護機制是否透過CK2-Nrf1細胞訊息路徑調控蛋白酶體活性，進而減少Mcl-1的降解速率。實驗結果顯示，轉染CK2α-EGFP DNA質體會增加Nrf1磷酸化並抑制蛋白酶體活性，泛素化之Mcl-1蛋白含量亦伴隨增加；轉染CK2α siRNA則會降低Nrf1磷酸化並促進蛋白酶體活性，導致naive Mcl-1蛋白質含量減少24小時的漢厚朴酚後處理（post-treatment）可以部份恢復因轉染CK2α siRNA所造成之CK2蛋白、Phosphoserine蛋白和Mcl-1蛋白質含量減少，在設計縮短間隔5小時漢厚朴酚後處理（post-treatment）的實驗結果雖然仍無法有效恢復CK2蛋白含量，但對於Phosphoserine和Mcl-1蛋白含量以及蛋白酶體活性則具有部份恢復的功效。利用過氧化氫造成細胞氧化壓力環境下，實驗發現間隔3小時的漢厚朴酚後處理才能有效恢復細胞存活率，間隔5小時的漢厚朴酚後處理則無法恢復細胞存活率。在大白鼠紋狀體腦區給予漢厚朴酚微量注射則對pTH、TH和GAD蛋白質含量皆有促進增加的作用，乙醯化的Histone H3蛋白含量也有顯著增加。綜合以上結果，推測漢厚朴酚對細胞保護作用的其中一個機制是參與調控CK2-Nrf1路徑而抑制蛋白酶體活性，減少Mcl-1蛋白質降解速率和提升氧化壓力下之細胞存活能力；此外，從活體動物的實驗結果顯示漢厚朴酚亦可能參與調控多巴胺和γ-氨基丁酸神經細胞功能的機制之中。
Honokiol is a natural compound, extracted from the Magnolia officinalis, and is known as its anti-oxidative, anti-inflammatory and neuroprotective effects. The previous study has been demonstrated that the honokiol can protect striatal dopamine neuron against 6-OHDA induced damage and reverse the apomorphine-induced rotational behavior in Parkinson’s disease model of rats. However, the cellular mechanisms for its neuroprotective effects are not fully investigated. Protein kinase Casine kinase 2 (CK2) is a serine/threonine kinase has a highly abundant expression in the striatum compared with other brain areas. Further, CK2 is shown to regulate many neuronal functions including neuroprotection. The nuclear factor E2-related factor 1 (Nrf1) has been identified as one of the substrate proteins for CK2 and is indicated to involve in the induction of proteasome subunits gene expressions in mouse embryonic fibroblasts. The anti-apoptotic protein myeloid cell leukemia 1 (Mcl-1) is shown to play a critical initiation role during the apoptosis process due to its synthesis blockage and proteasome degradation. The present study is aimed to investigate whether one of protective effects of honokiol is through CK2-mediated Nrf1 signaling pathway to regulate the proteasome activity in the mouse N2a neuroblastoma cell line. In the current results, transfection of the CK2α-EGFP plasmid DNA increased Nrf1 phosphorylation accompanied with the decrease in the proteasome activity but increased the ubiquitinated Mcl-1 protein. Whereas, transfection of CK2α siRNA decreased Nrf1 phosphorylation leading to the increase in proteasome activity and Mcl-1 protein degradation. The 24 hr duration of honokiol post-treatment only slightly reversed the knock-down effect of CK2α siRNA on CK2α and Mcl-1 protein levels. However, 5 hr duration of honokiol post-treatment could partially reverse the Mcl-1 protein level and proteasome activity but no effect on CK2α protein levels. In the H2O2-induced oxidative stress condition, only 3 hr duration of honokiol post-treatment could protect cells against H2O2-induced cell death. In the experiments of in vivo rat animal model, local administration of honokiol was found to increase phospho-TH, naive TH, GAD as well as acetylated Histone H3 protein levels. These above results suggest one of the protective mechanisms of honokiol might be through CK2-mediated Nrf1 signaling to inhibit the proteasome activity. and to promote cell survival under oxidative stress. Beside these functions, honokiol might also involve in the regulation of nurophysiological functions of dopamine and GABA neurons.
參考文獻 Adams JM (1998) The Bcl-2 Protein Family: Arbiters of Cell Survival. Science 281:1322-1326.
     Ahmed K, Gerber DA, Cochet C (2002) Joining the cell survival squad: an emerging role for protein kinase CK2. Trends in cell biology 12:226-230.
     Arbour N, Vanderluit JL, Le Grand JN, Jahani-Asl A, Ruzhynsky VA, Cheung EC, Kelly MA, MacKenzie AE, Park DS, Opferman JT (2008) Mcl-1 is a key regulator of apoptosis during CNS development and after DNA damage. The Journal of Neuroscience 28:6068-6078.
     Balasubramanian S, Kanade S, Han B, Eckert RL (2012) A proteasome inhibitor-stimulated Nrf1 protein-dependent compensatory increase in proteasome subunit gene expression reduces polycomb group protein level. The Journal of biological chemistry 287:36179-36189.
     Billen L, Shamas-Din A, Andrews D (2008) Bid: a Bax-like BH3 protein. Oncogene 27:S93-S104.
     Bouillet P, Metcalf D, Huang DC, Tarlinton DM, Kay TW, Köntgen F, Adams JM, Strasser A (1999) Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity. Science 286:1735-1738.
     Buchou T, Vernet M, Blond O, Jensen H, Pointu H, Olsen B, Cochet C, Issinger O (2003) Boldyreff. B.(2003) Disruption of the regulatory beta subunit of protein kinase CK2 in mice leads to a cell-autonomous defect and early embryonic lethality. Molecular and cellular biology 23:908-915.
     Candy S. Leea CL (2010) Loss of nuclear factor E2-related factor 1 in the brain
     leads to dysregulation of proteasome gene
     expression and neurodegeneration.
     Chan JY, Han X-L, Kan YW (1993) Cloning of Nrf1, an NF-E2-related transcription factor, by genetic selection in yeast. Proceedings of the National Academy of Sciences 90:11371-11375.
     Chan JY, Cheung M-C, Moi P, Chan K, Kan YW (1995) Chromosomal localization of the human NF-E2 family of bZIP transcription factors by fluorescence in situ hybridization. Human genetics 95:265-269.
     Chan JY, Kwong M, Lu R, Chang J, Wang B, Yen T, Kan YW (1998) Targeted disruption of the ubiquitous CNC‐bZIP transcription factor, Nrf‐1, results in anemia and embryonic lethality in mice. The EMBO journal 17:1779-1787.
     Chang-Mu C, Jen-Kun L, Shing-Hwa L, Shoei-Yn L-S (2010) Characterization of neurotoxic effects of NMDA and the novel neuroprotection by phytopolyphenols in mice. Behavioral neuroscience 124:541.
     Chang CM, Chao CC (2013) Protein kinase CK2 enhances Mcl-1 gene expression through the serum response factor-mediated pathway in the rat hippocampus. Journal of neuroscience research 91:808-817.
     Chao CC, Ma YL, Lee EH (2011) Brain-derived neurotrophic factor enhances Bcl-xL expression through protein kinase casein kinase 2-activated and nuclear factor kappa B-mediated pathway in rat hippocampus. Brain pathology 21:150-162.
     Chao CC, Chiang CH, Ma YL, Lee EH (2006) Molecular mechanism of the neurotrophic effect of GDNF on DA neurons: role of protein kinase CK2. Neurobiology of aging 27:105-118.
     Chen CM, Liu SH, Lin‐Shiau SY (2007) Honokiol, a Neuroprotectant against Mouse Cerebral Ischaemia, Mediated by Preserving Na+, K+‐ATPase Activity and Mitochondrial Functions. Basic & clinical pharmacology & toxicology 101:108-116.
     Chen L, Kwong M, Lu R, Ginzinger D, Lee C, Leung L, Chan JY (2003) Nrf1 is critical for redox balance and survival of liver cells during development. Molecular and cellular biology 23:4673-4686.
     Ciechanover A (1994) The ubiquitin-proteasome proteolytic pathway. Cell 79:13-21.
     Cory GO, Cramer R, Blanchoin L, Ridley AJ (2003) Phosphorylation of the WASP-VCA domain increases its affinity for the Arp2/3 complex and enhances actin polymerization by WASP. Molecular cell 11:1229-1239.
     Cuconati A, Mukherjee C, Perez D, White E (2003) DNA damage response and MCL-1 destruction initiate apoptosis in adenovirus-infected cells. Genes & development 17:2922-2932.
     Da Violante G, Zerrouk N, Richard I, Provot G, Chaumeil JC, Arnaud P (2002) Evaluation of the cytotoxicity effect of dimethyl sulfoxide (DMSO) on Caco2/TC7 colon tumor cell cultures. Biological and pharmaceutical bulletin 25:1600-1603.
     Davis AR, Lotocki G, Marcillo AE, Dietrich WD, Keane RW (2007) FasL, Fas, and death-inducing signaling complex (DISC) proteins are recruited to membrane rafts after spinal cord injury. Journal of neurotrauma 24:823-834.
     Derouet M, Thomas L, Cross A, Moots RJ, Edwards SW (2004) Granulocyte macrophage colony-stimulating factor signaling and proteasome inhibition delay neutrophil apoptosis by increasing the stability of Mcl-1. Journal of Biological Chemistry 279:26915-26921.
     Di Maira G, Salvi M, Arrigoni G, Marin O, Sarno S, Brustolon F, Pinna LA, Ruzzene M (2005) Protein kinase CK2 phosphorylates and upregulates Akt/PKB. Cell death and differentiation 12:668-677.
     Dominguez F, Chivez M, Gardun-Ramirez M, Chavez-Avila VM, Mata M, Cruz-Sosa F (2009) Production of honokiol and magnolol in suspension cultures of Magnolia dealbata Zucc. Nat Prod Commun 4:939-943.
     Dong E, Guidotti A, Grayson D, Costa E (2007) Histone hyperacetylation induces demethylation of reelin and 67-kDa glutamic acid decarboxylase promoters. Proceedings of the National Academy of Sciences 104:4676-4681.
     Eddy SF, Guo S, Demicco EG, Romieu-Mourez R, Landesman-Bollag E, Seldin DC, Sonenshein GE (2005) Inducible IκB kinase/IκB kinase ε expression is induced by CK2 and promotes aberrant nuclear factor-κB activation in breast cancer cells. Cancer research 65:11375-11383.
     Felten S, Olschowka J (1987) Noradrenergic sympathetic innervation of the spleen: II. Tyrosine hydroxylase (TH)‐positive nerve terminals form synapticlike contacts on lymphocytes in the splenic white pulp. Journal of neuroscience research 18:37-48.
     Fernández Murray P, Pardo PS, Zelada AM, Passeron S (2002) In vivo and in vitro phosphorylation of< i> Candida albicans 20S proteasome. Archives of biochemistry and biophysics 404:116-125.
     Galvao J, Davis B, Tilley M, Normando E, Duchen MR, Cordeiro MF (2014) Unexpected low-dose toxicity of the universal solvent DMSO. The FASEB Journal 28:1317-1330.
     Germain M, Nguyen AP, Le Grand JN, Arbour N, Vanderluit JL, Park DS, Opferman JT, Slack RS (2011) MCL‐1 is a stress sensor that regulates autophagy in a developmentally regulated manner. The EMBO journal 30:395-407.
     Gilad GM, Gilad VH (1991) Polyamines can protect against ischemia-induced nerve cell death in gerbil forebrain. Experimental neurology 111:349-355.
     Girault JA, Hemmings HC, Zorn SH, Gustafson EL, Greengard P (1990) Characterization in Mammalian Brain of a DARPP‐32 Serine Kinase Identical to Casein Kinase II. Journal of neurochemistry 55:1772-1783.
     Gong C, Shi S, Wang X, Wang Y, Fu S, Dong P, Chen L, Zhao X, Wei Y, Qian Z (2009) Novel Composite Drug Delivery System for Honokiol Delivery: Self-Assembled Poly (ethylene glycol)− Poly (ε-caprolactone)− Poly (ethylene glycol) Micelles in Thermosensitive Poly (ethylene glycol)− Poly (ε-caprolactone)− Poly (ethylene glycol) Hydrogel. The Journal of Physical Chemistry B 113:10183-10188.
     Grattan DR, Rocca MS, Strauss KI, Sagrillo CA, Selmanoff M, McCarthy MM (1996) GABAergic neuronal activity and mRNA levels for both forms of glutamic acid decarboxylase (GAD< sub> 65 and GAD< sub> 67) are reduced in the diagonal band of Broca during the afternoon of proestrus. Brain research 733:46-55.
     Gruppuso PA, Boylan JM (1995) Developmental changes in the activity and cellular localization of hepatic casein kinase II in the rat. Journal of cellular biochemistry 58:65-72.
     Guerra B, Issinger OG (1999) Protein kinase CK2 and its role in cellular proliferation, development and pathology. Electrophoresis 20:391-408.
     Guerra B, Siemer S, Boldyreff B, Issinger O-G (1999) Protein kinase CK2: evidence for a protein kinase CK2β subunit fraction, devoid of the catalytic CK2α subunit, in mouse brain and testicles. FEBS letters 462:353-357.
     Hakem R, Hakem A, Duncan GS, Henderson JT, Woo M, Soengas MS, Elia A, de la Pompa JL, Kagi D, Khoo W (1998) Differential requirement for caspase 9 in apoptotic pathways in vivo. Cell 94:339-352.
     Hathaway G, Traugh J (1981) Casein kinases--multipotential protein kinases. Current topics in cellular regulation 21:101-127.
     Hessenauer A, Schneider CC, Götz C, Montenarh M (2011) CK2 inhibition induces apoptosis via the ER stress response. Cellular signalling 23:145-151.
     Hu BR, Wieloch T (1993) Casein kinase II activity in the postischemic rat brain increases in brain regions resistant to ischemia and decreases in vulnerable areas. Journal of neurochemistry 60:1722-1728.
     Hu Z, Bian X, Liu X, Zhu Y, Zhang X, Chen S, Wang K, Wang Y (2013) Honokiol protects brain against ischemia-reperfusion injury in rats through disrupting PSD95-nNOS interaction. Brain research 1491:204-212.
     Iimoto DS, Masliah E, DeTeresa R, Terry RD, Saitoh T (1990) Aberrant casein kinase II in Alzheimer`s disease. Brain research 507:273-280.
     Iyer SS, Pulskens WP, Sadler JJ, Butter LM, Teske GJ, Ulland TK, Eisenbarth SC, Florquin S, Flavell RA, Leemans JC (2009) Necrotic cells trigger a sterile inflammatory response through the Nlrp3 inflammasome. Proceedings of the National Academy of Sciences 106:20388-20393.
     Klebe R, Ruddle R (1969) Neuroblastoma-Cell culture analysis of a differentiating stem cell system. In: Journal of Cell Biology, pp A69-&: ROCKEFELLER UNIV PRESS 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021.
     Kobayashi A, Tsukide T, Miyasaka T, Morita T, Mizoroki T, Saito Y, Ihara Y, Takashima A, Noguchi N, Fukamizu A, Hirotsu Y, Ohtsuji M, Katsuoka F, Yamamoto M (2011) Central nervous system-specific deletion of transcription factor Nrf1 causes progressive motor neuronal dysfunction. Genes to cells : devoted to molecular & cellular mechanisms 16:692-703.
     Kozopas KM, Yang T, Buchan HL, Zhou P, Craig RW (1993) MCL1, a gene expressed in programmed myeloid cell differentiation, has sequence similarity to BCL2. Proceedings of the National Academy of Sciences 90:3516-3520.
     Ku TH, Lee YJ, Wang SJ, Fan CH, Tien LT (2011) Effect of honokiol on activity of GAD(65) and GAD(67) in the cortex and hippocampus of mice. Phytomedicine : international journal of phytotherapy and phytopharmacology 18:1126-1129.
     Kuwana T, Bouchier-Hayes L, Chipuk JE, Bonzon C, Sullivan BA, Green DR, Newmeyer DD (2005) BH3 domains of BH3-only proteins differentially regulate Bax-mediated mitochondrial membrane permeabilization both directly and indirectly. Molecular cell 17:525-535.
     Lecker SH, Goldberg AL, Mitch WE (2006) Protein degradation by the ubiquitin–proteasome pathway in normal and disease states. Journal of the American Society of Nephrology 17:1807-1819.
     Lee CS, Lee C, Hu T, Nguyen JM, Zhang J, Martin MV, Vawter MP, Huang EJ, Chan JY (2011) Loss of nuclear factor E2-related factor 1 in the brain leads to dysregulation of proteasome gene expression and neurodegeneration. Proceedings of the National Academy of Sciences 108:8408-8413.
     Letai A, Bassik MC, Walensky LD, Sorcinelli MD, Weiler S, Korsmeyer SJ (2002) Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics. Cancer cell 2:183-192.
     Li D, Chen XQ, Li W-J, Yang Y-H, Wang J-Z, Yu ACH (2007) Cytoglobin up-regulated by hydrogen peroxide plays a protective role in oxidative stress. Neurochemical research 32:1375-1380.
     Lin J-W, Chen J-T, Hong C-Y, Lin Y-L, Wang K-T, Yao C-J, Lai G-M, Chen R-M (2012) Honokiol traverses the blood-brain barrier and induces apoptosis of neuroblastoma cells via an intrinsic bax-mitochondrion-cytochrome c-caspase protease pathway. Neuro-oncology 14:302-314.
     Loizou JI, El-Khamisy SF, Zlatanou A, Moore DJ, Chan DW, Qin J, Sarno S, Meggio F, Pinna LA, Caldecott KW (2004) The protein kinase CK2 facilitates repair of chromosomal DNA single-strand breaks. Cell 117:17-28.
     Lou DY, Dominguez I, Toselli P, Landesman-Bollag E, O`Brien C, Seldin DC (2008) The alpha catalytic subunit of protein kinase CK2 is required for mouse embryonic development. Molecular and cellular biology 28:131-139.
     Luis Ulloa (1993) Depletion of casein kinase 11 by antisense oligonucleotide prevents neuritogenesis in neuroblastoma cells.
     Matsui N, Takahashi K, Takeichi M, Kuroshita T, Noguchi K, Yamazaki K, Tagashira H, Tsutsui K, Okada H, Kido Y (2009) Magnolol and honokiol prevent learning and memory impairment and cholinergic deficit in SAMP8 mice. Brain research 1305:108-117.
     Meggio F, PINNA LA (2003) One-thousand-and-one substrates of protein kinase CK2? The FASEB Journal 17:349-368.
     Mori M, Burgess D, Gefrides L, Foreman P, Opferman J, Korsmeyer S, Cavalheiro E, Naffah-Mazzacoratti MG, Noebels J (2004) Expression of apoptosis inhibitor protein Mcl1 linked to neuroprotection in CNS neurons. Cell Death & Differentiation 11:1223-1233.
     Narayanan K, Ramachandran A, Peterson MC, Hao J, Kolstø A-B, Friedman AD, George A (2004) The CCAAT enhancer-binding protein (C/EBP) β and Nrf1 interact to regulate dentin sialophosphoprotein (DSPP) gene expression during odontoblast differentiation. Journal of Biological Chemistry 279:45423-45432.
     Nencioni A, Hua F, Dillon CP, Yokoo R, Scheiermann C, Cardone MH, Barbieri E, Rocco I, Garuti A, Wesselborg S (2005) Evidence for a protective role of Mcl-1 in proteasome inhibitor-induced apoptosis. Blood 105:3255-3262.
     Nijhawan D, Fang M, Traer E, Zhong Q, Gao W, Du F, Wang X (2003) Elimination of Mcl-1 is required for the initiation of apoptosis following ultraviolet irradiation. Genes & development 17:1475-1486.
     Nikolai L. Chepelev JDB, Ting Huang, Skye McBride, William G. Willmore (2011) The Nrf1 CNC-bZIP Protein Is Regulated by the
     Proteasome and Activated by Hypoxia.
     Okoumassoun LE, Russo C, Denizeau F, Averill‐Bates D, Henderson D, Janet E (2007) Parathyroid hormone‐related protein (PTHrP) inhibits mitochondrial‐dependent apoptosis through CK2. Journal of cellular physiology 212:591-599.
     Opferman JT, Letai A, Beard C, Sorcinelli MD, Ong CC, Korsmeyer SJ (2003) Development and maintenance of B and T lymphocytes requires antiapoptotic MCL-1. Nature 426:671-676.
     Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinatesAcademic Press. New York:55-60.
     Pepperkok R, Lorenz P, Jakobi R, Ansorge W, Pyerin W (1991) Cell growth stimulation by EGF: inhibition through antisense-oligodeoxynucleotides demonstrates important role of casein kinase II. Experimental cell research 197:245-253.
     Perciavalle RM, Stewart DP, Koss B, Lynch J, Milasta S, Bathina M, Temirov J, Cleland MM, Pelletier S, Schuetz JD (2012) Anti-apoptotic MCL-1 localizes to the mitochondrial matrix and couples mitochondrial fusion to respiration. Nature cell biology 14:575-583.
     Pi J, Bai Y, Reece JM, Williams J, Liu D, Freeman ML, Fahl WE, Shugar D, Liu J, Qu W (2007) Molecular mechanism of human Nrf2 activation and degradation: role of sequential phosphorylation by protein kinase CK2. Free Radical Biology and Medicine 42:1797-1806.
     Pinna LA (1990) Casein kinase 2: an ‘eminence grise’in cellular regulation? Biochimica et Biophysica Acta (BBA)-Molecular Cell Research 1054:267-284.
     Préville X, Gaestel M, Arrigo A-P (1998) Phosphorylation is not essential for protection of L929 cells by Hsp25 against H2O2-mediated disruption actin cytoskeleton, a protection which appears related to the redox change mediated by Hsp25. Cell stress & chaperones 3:177.
     Qu WM, Yue XF, Sun Y, Fan K, Chen CR, Hou YP, Urade Y, Huang ZL (2012) Honokiol promotes non-rapid eye movement sleep via the benzodiazepine site of the GABA(A) receptor in mice. British journal of pharmacology 167:587-598.
     Radhakrishnan SK, Lee CS, Young P, Beskow A, Chan JY, Deshaies RJ (2010) Transcription factor Nrf1 mediates the proteasome recovery pathway after proteasome inhibition in mammalian cells. Molecular cell 38:17-28.
     Rebholz H, Zhou M, Nairn AC, Greengard P, Flajolet M (2013) Selective knockout of the casein kinase 2 in d1 medium spiny neurons controls dopaminergic function. Biological psychiatry 74:113-121.
     Rinkenberger JL, Horning S, Klocke B, Roth K, Korsmeyer SJ (2000) Mcl-1 deficiency results in peri-implantation embryonic lethality. Genes & development 14:23-27.
     Romieu-Mourez R, Landesman-Bollag E, Seldin DC, Sonenshein GE (2002) Protein kinase CK2 promotes aberrant activation of nuclear factor-κB, transformed phenotype, and survival of breast cancer cells. Cancer research 62:6770-6778.
     Ruzzene M, Penzo D, Pinna L (2002) Protein kinase CK2 inhibitor 4, 5, 6, 7-tetrabromobenzotriazole (TBB) induces apoptosis and caspase-dependent degradation of haematopoietic lineage cell-specific protein 1 (HS1) in Jurkat cells. Biochem J 364:41-47.
     Salvesen GS, Dixit VM (1997) Caspases: intracellular signaling by proteolysis. Cell 91:443-446.
     Satoh T, Harada N, Hosoya T, Tohyama K, Yamamoto M, Itoh K (2009) Keap1/Nrf2 system regulates neuronal survival as revealed through study of< i> keap1 gene-knockout mice. Biochemical and biophysical research communications 380:298-302.
     Schultz MA, Abdel-Mageed AB, Mondal D (2010) The Nrf1 and Nrf2 balance in oxidative stress regulation and androgen signaling in prostate cancer cells. Cancers 2:1354-1378.
     Semplici F, Meggio F, Pinna LA, Oliviero S (2002) CK2-dependent phosphorylation of the E2 ubiquitin conjugating enzyme UBC3B induces its interaction with b-TrCP and enhances b-catenin degradation. Oncogene 21:3978-3987.
     Shi Y (2006) Mechanical aspects of apoptosome assembly. Current opinion in cell biology 18:677-684.
     Srinivasula SM, Hegde R, Saleh A, Datta P, Shiozaki E, Chai J, Lee R-A, Robbins PD, Fernandes-Alnemri T, Shi Y (2001) A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis. Nature 410:112-116.
     Tang X, Yao K, Zhang L, Yang Y, Yao H (2011) Honokiol inhibits H(2)O(2)-induced apoptosis in human lens epithelial cells via inhibition of the mitogen-activated protein kinase and Akt pathways. European journal of pharmacology 650:72-78.
     Thomas LW, Lam C, Edwards SW (2010) Mcl-1; the molecular regulation of protein function. FEBS Lett 584:2981-2989.
     Tilly JL, Kolesnick RN (2002) Sphingolipids, apoptosis, cancer treatments and the ovary: investigating a crime against female fertility. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids 1585:135-138.
     Tsuchiya Y (2013) The Casein Kinase 2-Nrf1 Axis Controls the Clearance of
     Ubiquitinated Proteins by Regulating Proteasome Gene Expression.
     Ulery PG, Rudenko G, Nestler EJ (2006) Regulation of ΔFosB stability by phosphorylation. The Journal of neuroscience 26:5131-5142.
     Wang G, Ahmad KA, Ahmed K (2006) Role of protein kinase CK2 in the regulation of tumor necrosis factor-related apoptosis inducing ligand-induced apoptosis in prostate cancer cells. Cancer research 66:2242-2249.
     Wang W, Kwok AM, Chan JY (2007) The p65 isoform of Nrf1 is a dominant negative inhibitor of ARE-mediated transcription. The Journal of biological chemistry 282:24670-24678.
     Wang X (2001) The expanding role of mitochondria in apoptosis. Genes & development 15:2922-2933.
     Wang Y, Sun W, Du B, Miao X, Bai Y, Xin Y, Tan Y, Cui W, Liu B, Cui T (2013) Therapeutic effect of MG-132 on diabetic cardiomyopathy is associated with its suppression of proteasomal activities: roles of Nrf2 and NF-κB. American Journal of Physiology-Heart and Circulatory Physiology 304:H567-H578.
     Wei MC, Zong W-X, Cheng EH-Y, Lindsten T, Panoutsakopoulou V, Ross AJ, Roth KA, MacGregor GR, Thompson CB, Korsmeyer SJ (2001) Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 292:727-730.
     Willis SN, Fletcher JI, Kaufmann T, van Delft MF, Chen L, Czabotar PE, Ierino H, Lee EF, Fairlie WD, Bouillet P (2007) Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak. Science 315:856-859.
     Woodbury A, Yu SP, Wei L, Garcia P (2013) Neuro-modulating effects of honokiol: a review. Frontiers in neurology 4:130.
     Xu X, Toselli PA, Russell LD, Seldin DC (1999) Globozoospermia in mice lacking the casein kinase II α′ catalytic subunit. Nature genetics 23:118-121.
     Yang E, Zha J, Jockel J, Boise LH, Thompson CB, Korsmeyer SJ (1995) Bad, a heterodimeric partner for Bcl-x< sub> L and Bcl-2, displaces bax and promotes cell death. Cell 80:285-291.
     Yin X-M, Wang K, Gross A, Zhao Y, Zinkel S, Klocke B, Roth KA, Korsmeyer SJ (1999) Bid-deficient mice are resistant to Fas-induced hepatocellular apoptosis. Nature 400:886-891.
     Youle RJ (2007) Cellular demolition and the rules of engagement. Science 315:776-777.
     Zhai H, Nakade K, Oda M, Mitsumoto Y, Akagi M, Sakurai J, Fukuyama Y (2005) Honokiol-induced neurite outgrowth promotion depends on activation of extracellular signal-regulated kinases (ERK1/2). European journal of pharmacology 516:112-117.
     Zhang J, D`Ercole AJ (2004) Expression of Mcl-1 in cerebellar granule neurons is regulated by IGF-I in a developmentally specific fashion. Developmental brain research 152:255-263.
     Zhang P, Liu X, Zhu Y, Chen S, Zhou D, Wang Y (2013) Honokiol inhibits the inflammatory reaction during cerebral ischemia reperfusion by suppressing NF-κB activation and cytokine production of glial cells. Neuroscience letters 534:123-127.
     Zhang Y, Lucocq JM, Hayes JD (2009a) The Nrf1 CNC/bZIP protein is a nuclear envelope-bound transcription factor that is activated by t-butyl hydroquinone but not by endoplasmic reticulum stressors. The Biochemical journal 418:293-310.
     Zhang Y, Lucocq J, Hayes J (2009b) The Nrf1 CNC/bZIP protein is a nuclear envelope-bound transcription factor that is activated by t-butyl hydroquinone but not by endoplasmic reticulum stressors. Biochem J 418:293-310.
     Zhang Y, Lucocq J, Yamamoto M, Hayes J (2007) The NHB1 (N-terminal homology box 1) sequence in transcription factor Nrf1 is required to anchor it to the endoplasmic reticulum and also to enable its asparagine-glycosylation. Biochem J 408:161-172.
描述 碩士
國立政治大學
神經科學研究所
101754006
102
資料來源 http://thesis.lib.nccu.edu.tw/record/#G0101754006
資料類型 thesis
dc.contributor.advisor 趙知章zh_TW
dc.contributor.advisor Chao, Chih Changen_US
dc.contributor.author (Authors) 吳芊澐zh_TW
dc.creator (作者) 吳芊澐zh_TW
dc.date (日期) 2013en_US
dc.date.accessioned 1-Sep-2014 13:48:34 (UTC+8)-
dc.date.available 1-Sep-2014 13:48:34 (UTC+8)-
dc.date.issued (上傳時間) 1-Sep-2014 13:48:34 (UTC+8)-
dc.identifier (Other Identifiers) G0101754006en_US
dc.identifier.uri (URI) http://nccur.lib.nccu.edu.tw/handle/140.119/69457-
dc.description (描述) 碩士zh_TW
dc.description (描述) 國立政治大學zh_TW
dc.description (描述) 神經科學研究所zh_TW
dc.description (描述) 101754006zh_TW
dc.description (描述) 102zh_TW
dc.description.abstract (摘要) 漢厚朴酚是從木蘭科植物中萃取之天然化合物，已知具有抗氧化、抗發炎及神經保護之生理活性功能。先前的研究證明漢厚朴酚可以保護多巴胺神經元對抗6-OHDA所引起的細胞傷害，並且可以減緩6-OHDA 動物模式由apomorphine所誘發的旋轉行為，但漢厚朴酚對於神經保護之分子機制的相關研究尚未釐清。蛋白激酶CK2是具有多功能的絲氨酸/蘇氨酸激酶，高度表現在大腦紋狀體中，先前的研究證實蛋白激酶CK2參與調節神經系統功能和具有神經保護之作用。先前研究也指出轉錄因子Nrf1（Nuclear factor E2-related factor 1）是蛋白激酶CK2下游磷酸化受質，會調控小鼠胚胎纖維細胞中蛋白酶體基因的表現。抗細胞凋亡蛋白Mcl-1 (myeloid cell leukemia 1) 屬於Bcl-2蛋白家族的成員之一，在細胞凋亡的過程中，其蛋白含量減少與細胞凋亡有密切關聯性，抑制Mcl-1蛋白的降解可以延遲細胞死亡。因此本論文主要探討漢厚朴酚的神經細胞保護機制是否透過CK2-Nrf1細胞訊息路徑調控蛋白酶體活性，進而減少Mcl-1的降解速率。實驗結果顯示，轉染CK2α-EGFP DNA質體會增加Nrf1磷酸化並抑制蛋白酶體活性，泛素化之Mcl-1蛋白含量亦伴隨增加；轉染CK2α siRNA則會降低Nrf1磷酸化並促進蛋白酶體活性，導致naive Mcl-1蛋白質含量減少24小時的漢厚朴酚後處理（post-treatment）可以部份恢復因轉染CK2α siRNA所造成之CK2蛋白、Phosphoserine蛋白和Mcl-1蛋白質含量減少，在設計縮短間隔5小時漢厚朴酚後處理（post-treatment）的實驗結果雖然仍無法有效恢復CK2蛋白含量，但對於Phosphoserine和Mcl-1蛋白含量以及蛋白酶體活性則具有部份恢復的功效。利用過氧化氫造成細胞氧化壓力環境下，實驗發現間隔3小時的漢厚朴酚後處理才能有效恢復細胞存活率，間隔5小時的漢厚朴酚後處理則無法恢復細胞存活率。在大白鼠紋狀體腦區給予漢厚朴酚微量注射則對pTH、TH和GAD蛋白質含量皆有促進增加的作用，乙醯化的Histone H3蛋白含量也有顯著增加。綜合以上結果，推測漢厚朴酚對細胞保護作用的其中一個機制是參與調控CK2-Nrf1路徑而抑制蛋白酶體活性，減少Mcl-1蛋白質降解速率和提升氧化壓力下之細胞存活能力；此外，從活體動物的實驗結果顯示漢厚朴酚亦可能參與調控多巴胺和γ-氨基丁酸神經細胞功能的機制之中。zh_TW
dc.description.abstract (摘要) Honokiol is a natural compound, extracted from the Magnolia officinalis, and is known as its anti-oxidative, anti-inflammatory and neuroprotective effects. The previous study has been demonstrated that the honokiol can protect striatal dopamine neuron against 6-OHDA induced damage and reverse the apomorphine-induced rotational behavior in Parkinson’s disease model of rats. However, the cellular mechanisms for its neuroprotective effects are not fully investigated. Protein kinase Casine kinase 2 (CK2) is a serine/threonine kinase has a highly abundant expression in the striatum compared with other brain areas. Further, CK2 is shown to regulate many neuronal functions including neuroprotection. The nuclear factor E2-related factor 1 (Nrf1) has been identified as one of the substrate proteins for CK2 and is indicated to involve in the induction of proteasome subunits gene expressions in mouse embryonic fibroblasts. The anti-apoptotic protein myeloid cell leukemia 1 (Mcl-1) is shown to play a critical initiation role during the apoptosis process due to its synthesis blockage and proteasome degradation. The present study is aimed to investigate whether one of protective effects of honokiol is through CK2-mediated Nrf1 signaling pathway to regulate the proteasome activity in the mouse N2a neuroblastoma cell line. In the current results, transfection of the CK2α-EGFP plasmid DNA increased Nrf1 phosphorylation accompanied with the decrease in the proteasome activity but increased the ubiquitinated Mcl-1 protein. Whereas, transfection of CK2α siRNA decreased Nrf1 phosphorylation leading to the increase in proteasome activity and Mcl-1 protein degradation. The 24 hr duration of honokiol post-treatment only slightly reversed the knock-down effect of CK2α siRNA on CK2α and Mcl-1 protein levels. However, 5 hr duration of honokiol post-treatment could partially reverse the Mcl-1 protein level and proteasome activity but no effect on CK2α protein levels. In the H2O2-induced oxidative stress condition, only 3 hr duration of honokiol post-treatment could protect cells against H2O2-induced cell death. In the experiments of in vivo rat animal model, local administration of honokiol was found to increase phospho-TH, naive TH, GAD as well as acetylated Histone H3 protein levels. These above results suggest one of the protective mechanisms of honokiol might be through CK2-mediated Nrf1 signaling to inhibit the proteasome activity. and to promote cell survival under oxidative stress. Beside these functions, honokiol might also involve in the regulation of nurophysiological functions of dopamine and GABA neurons.en_US
dc.description.tableofcontents 目錄
     謝 誌 II
     中文摘要 IIV
     英文摘要 V
     目 錄 VII
     圖 次 IX
     縮寫對照表 X
     第一章 緒 論 1
     第一節 漢厚朴酚 ( Honokiol ) 2
     第二節 蛋白激酶CK2（Protein kinase CK2, Casein kinase 2） 5
     第三節 轉錄因子蛋白Nrf1（Nuclear factor E2-related factor 1） 8
     第四節 計畫性的細胞凋亡（Apoptosis） 10
     第五節 抗細胞凋亡蛋白Bcl-2 (B-cell lymphoma-2) 家族 12
     一. Bcl-2 (B-cell lymphoma-2)家族 12
     二. Mcl-1 (myeloid cell leukemia 1) 12
     第六節 論文之研究目的及策略 15
     第二章 材料方法 16
     第一節 細胞培養 17
     一. 細胞培養 17
     二. 細胞繼代培養與計數 17
     第二節 實驗動物 18
     第三節 立體定位手術（stereotaxic surgey） 18
     第四節 小量DNA製備 19
     第五節 瓊脂膠體電泳分析 19
     第六節 細胞轉染 19
     第七節 藥物處理 20
     第八節 西方點墨法 21
     一. 蛋白質萃取 21
     二. 蛋白質濃度測定 21
     三. 樣品配製 22
     四. 鑄膠和聚丙烯醯胺膠體電泳 (Sodium dodecyl sulfate polyacrylamide gel electrophoresis,SDS-PAGE) 22
     五. 轉漬（Transfer） 22
     六. 免疫轉印（Immunoblotting） 23
     第九節 免疫沉澱法（Immunoprecipitation, IP） 24
     第十節 細胞存活試驗－MTT試驗法（MTT assay） 24
     第十一節 蛋白酶體活性測試（proteasome activity） 25
     第十二節 統計分析 26
     第三章 實驗結果 27
     第一節 操弄蛋白激酶CK2α 基因表現對Nrf1、Mcl-1蛋白質含量及蛋白酶體活性的影響 28
     一、轉染CK2α-EGFP 質體DNA對Nrf1、Mcl-1蛋白質含量及蛋白酶體活性的影響 28
     二．轉染CK2α siRNA 對Nrf1、Mcl-1蛋白質含量及蛋白酶體活性的影響 35
     第二節 漢厚朴酚後處理（post-treatment）和CK2α siRNA轉染或過氧化氫處理對細胞蛋白質表現量、蛋白酶體活性和細胞凋亡的影響 41
     一、漢厚朴酚間隔24小時之後處理（post-treatment）和CK2α siRNA 轉染處理對細胞蛋白質表現量的影響 41
     二、漢厚朴酚間隔16小時之後處理（post-treatment）和過氧化氫處理對細胞凋亡的影響 44
     三、 漢厚朴酚間隔5小時之後處理（post-treatment）和CK2α siRNA 轉染處理對細胞蛋白質表現量的影響 46
     四、漢厚朴酚間隔不同時間之後處理（post-treatment）和過氧化氫處理對細胞凋亡的影響 50
     五、漢厚朴酚間隔三小時後處理（post-treatment）對過氧化氫處理之細胞蛋白質表現量的影響 52
     六、CK2α siRNA對細胞Nrf1 65 kDa蛋白質表現量的影響 55
     第三節 漢厚朴酚處理對大白鼠紋狀體腦區蛋白質含量改變的影響 57
     第四章 討論 60
     第五章 結論 66		zh_TW
dc.language.iso en_US-
dc.source.uri (資料來源) http://thesis.lib.nccu.edu.tw/record/#G0101754006en_US
dc.subject (關鍵詞) 漢厚朴酚zh_TW
dc.subject (關鍵詞) 蛋白激酶 CK2zh_TW
dc.subject (關鍵詞) Nrf1 蛋白zh_TW
dc.subject (關鍵詞) 抗細胞凋亡Mcl -1蛋白zh_TW
dc.subject (關鍵詞) 蛋白酶體活性zh_TW
dc.subject (關鍵詞) Honokiolen_US
dc.subject (關鍵詞) protein kinase CK2en_US
dc.subject (關鍵詞) Nrf1en_US
dc.subject (關鍵詞) Mcl-1en_US
dc.subject (關鍵詞) proteasome activityen_US
dc.title (題名) 漢厚朴酚與蛋白激酶 CK2 的交互作用對 Nrf1 蛋白調控蛋 白酶體活性的影響zh_TW
dc.title (題名) The interactive effects of honokiol and protein kinase CK2α on the Nrf1-mediated proteasome activityen_US
dc.type (資料類型) thesisen
dc.relation.reference (參考文獻) Adams JM (1998) The Bcl-2 Protein Family: Arbiters of Cell Survival. Science 281:1322-1326.
     Ahmed K, Gerber DA, Cochet C (2002) Joining the cell survival squad: an emerging role for protein kinase CK2. Trends in cell biology 12:226-230.
     Arbour N, Vanderluit JL, Le Grand JN, Jahani-Asl A, Ruzhynsky VA, Cheung EC, Kelly MA, MacKenzie AE, Park DS, Opferman JT (2008) Mcl-1 is a key regulator of apoptosis during CNS development and after DNA damage. The Journal of Neuroscience 28:6068-6078.
     Balasubramanian S, Kanade S, Han B, Eckert RL (2012) A proteasome inhibitor-stimulated Nrf1 protein-dependent compensatory increase in proteasome subunit gene expression reduces polycomb group protein level. The Journal of biological chemistry 287:36179-36189.
     Billen L, Shamas-Din A, Andrews D (2008) Bid: a Bax-like BH3 protein. Oncogene 27:S93-S104.
     Bouillet P, Metcalf D, Huang DC, Tarlinton DM, Kay TW, Köntgen F, Adams JM, Strasser A (1999) Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity. Science 286:1735-1738.
     Buchou T, Vernet M, Blond O, Jensen H, Pointu H, Olsen B, Cochet C, Issinger O (2003) Boldyreff. B.(2003) Disruption of the regulatory beta subunit of protein kinase CK2 in mice leads to a cell-autonomous defect and early embryonic lethality. Molecular and cellular biology 23:908-915.
     Candy S. Leea CL (2010) Loss of nuclear factor E2-related factor 1 in the brain
     leads to dysregulation of proteasome gene
     expression and neurodegeneration.
     Chan JY, Han X-L, Kan YW (1993) Cloning of Nrf1, an NF-E2-related transcription factor, by genetic selection in yeast. Proceedings of the National Academy of Sciences 90:11371-11375.
     Chan JY, Cheung M-C, Moi P, Chan K, Kan YW (1995) Chromosomal localization of the human NF-E2 family of bZIP transcription factors by fluorescence in situ hybridization. Human genetics 95:265-269.
     Chan JY, Kwong M, Lu R, Chang J, Wang B, Yen T, Kan YW (1998) Targeted disruption of the ubiquitous CNC‐bZIP transcription factor, Nrf‐1, results in anemia and embryonic lethality in mice. The EMBO journal 17:1779-1787.
     Chang-Mu C, Jen-Kun L, Shing-Hwa L, Shoei-Yn L-S (2010) Characterization of neurotoxic effects of NMDA and the novel neuroprotection by phytopolyphenols in mice. Behavioral neuroscience 124:541.
     Chang CM, Chao CC (2013) Protein kinase CK2 enhances Mcl-1 gene expression through the serum response factor-mediated pathway in the rat hippocampus. Journal of neuroscience research 91:808-817.
     Chao CC, Ma YL, Lee EH (2011) Brain-derived neurotrophic factor enhances Bcl-xL expression through protein kinase casein kinase 2-activated and nuclear factor kappa B-mediated pathway in rat hippocampus. Brain pathology 21:150-162.
     Chao CC, Chiang CH, Ma YL, Lee EH (2006) Molecular mechanism of the neurotrophic effect of GDNF on DA neurons: role of protein kinase CK2. Neurobiology of aging 27:105-118.
     Chen CM, Liu SH, Lin‐Shiau SY (2007) Honokiol, a Neuroprotectant against Mouse Cerebral Ischaemia, Mediated by Preserving Na+, K+‐ATPase Activity and Mitochondrial Functions. Basic & clinical pharmacology & toxicology 101:108-116.
     Chen L, Kwong M, Lu R, Ginzinger D, Lee C, Leung L, Chan JY (2003) Nrf1 is critical for redox balance and survival of liver cells during development. Molecular and cellular biology 23:4673-4686.
     Ciechanover A (1994) The ubiquitin-proteasome proteolytic pathway. Cell 79:13-21.
     Cory GO, Cramer R, Blanchoin L, Ridley AJ (2003) Phosphorylation of the WASP-VCA domain increases its affinity for the Arp2/3 complex and enhances actin polymerization by WASP. Molecular cell 11:1229-1239.
     Cuconati A, Mukherjee C, Perez D, White E (2003) DNA damage response and MCL-1 destruction initiate apoptosis in adenovirus-infected cells. Genes & development 17:2922-2932.
     Da Violante G, Zerrouk N, Richard I, Provot G, Chaumeil JC, Arnaud P (2002) Evaluation of the cytotoxicity effect of dimethyl sulfoxide (DMSO) on Caco2/TC7 colon tumor cell cultures. Biological and pharmaceutical bulletin 25:1600-1603.
     Davis AR, Lotocki G, Marcillo AE, Dietrich WD, Keane RW (2007) FasL, Fas, and death-inducing signaling complex (DISC) proteins are recruited to membrane rafts after spinal cord injury. Journal of neurotrauma 24:823-834.
     Derouet M, Thomas L, Cross A, Moots RJ, Edwards SW (2004) Granulocyte macrophage colony-stimulating factor signaling and proteasome inhibition delay neutrophil apoptosis by increasing the stability of Mcl-1. Journal of Biological Chemistry 279:26915-26921.
     Di Maira G, Salvi M, Arrigoni G, Marin O, Sarno S, Brustolon F, Pinna LA, Ruzzene M (2005) Protein kinase CK2 phosphorylates and upregulates Akt/PKB. Cell death and differentiation 12:668-677.
     Dominguez F, Chivez M, Gardun-Ramirez M, Chavez-Avila VM, Mata M, Cruz-Sosa F (2009) Production of honokiol and magnolol in suspension cultures of Magnolia dealbata Zucc. Nat Prod Commun 4:939-943.
     Dong E, Guidotti A, Grayson D, Costa E (2007) Histone hyperacetylation induces demethylation of reelin and 67-kDa glutamic acid decarboxylase promoters. Proceedings of the National Academy of Sciences 104:4676-4681.
     Eddy SF, Guo S, Demicco EG, Romieu-Mourez R, Landesman-Bollag E, Seldin DC, Sonenshein GE (2005) Inducible IκB kinase/IκB kinase ε expression is induced by CK2 and promotes aberrant nuclear factor-κB activation in breast cancer cells. Cancer research 65:11375-11383.
     Felten S, Olschowka J (1987) Noradrenergic sympathetic innervation of the spleen: II. Tyrosine hydroxylase (TH)‐positive nerve terminals form synapticlike contacts on lymphocytes in the splenic white pulp. Journal of neuroscience research 18:37-48.
     Fernández Murray P, Pardo PS, Zelada AM, Passeron S (2002) In vivo and in vitro phosphorylation of< i> Candida albicans 20S proteasome. Archives of biochemistry and biophysics 404:116-125.
     Galvao J, Davis B, Tilley M, Normando E, Duchen MR, Cordeiro MF (2014) Unexpected low-dose toxicity of the universal solvent DMSO. The FASEB Journal 28:1317-1330.
     Germain M, Nguyen AP, Le Grand JN, Arbour N, Vanderluit JL, Park DS, Opferman JT, Slack RS (2011) MCL‐1 is a stress sensor that regulates autophagy in a developmentally regulated manner. The EMBO journal 30:395-407.
     Gilad GM, Gilad VH (1991) Polyamines can protect against ischemia-induced nerve cell death in gerbil forebrain. Experimental neurology 111:349-355.
     Girault JA, Hemmings HC, Zorn SH, Gustafson EL, Greengard P (1990) Characterization in Mammalian Brain of a DARPP‐32 Serine Kinase Identical to Casein Kinase II. Journal of neurochemistry 55:1772-1783.
     Gong C, Shi S, Wang X, Wang Y, Fu S, Dong P, Chen L, Zhao X, Wei Y, Qian Z (2009) Novel Composite Drug Delivery System for Honokiol Delivery: Self-Assembled Poly (ethylene glycol)− Poly (ε-caprolactone)− Poly (ethylene glycol) Micelles in Thermosensitive Poly (ethylene glycol)− Poly (ε-caprolactone)− Poly (ethylene glycol) Hydrogel. The Journal of Physical Chemistry B 113:10183-10188.
     Grattan DR, Rocca MS, Strauss KI, Sagrillo CA, Selmanoff M, McCarthy MM (1996) GABAergic neuronal activity and mRNA levels for both forms of glutamic acid decarboxylase (GAD< sub> 65 and GAD< sub> 67) are reduced in the diagonal band of Broca during the afternoon of proestrus. Brain research 733:46-55.
     Gruppuso PA, Boylan JM (1995) Developmental changes in the activity and cellular localization of hepatic casein kinase II in the rat. Journal of cellular biochemistry 58:65-72.
     Guerra B, Issinger OG (1999) Protein kinase CK2 and its role in cellular proliferation, development and pathology. Electrophoresis 20:391-408.
     Guerra B, Siemer S, Boldyreff B, Issinger O-G (1999) Protein kinase CK2: evidence for a protein kinase CK2β subunit fraction, devoid of the catalytic CK2α subunit, in mouse brain and testicles. FEBS letters 462:353-357.
     Hakem R, Hakem A, Duncan GS, Henderson JT, Woo M, Soengas MS, Elia A, de la Pompa JL, Kagi D, Khoo W (1998) Differential requirement for caspase 9 in apoptotic pathways in vivo. Cell 94:339-352.
     Hathaway G, Traugh J (1981) Casein kinases--multipotential protein kinases. Current topics in cellular regulation 21:101-127.
     Hessenauer A, Schneider CC, Götz C, Montenarh M (2011) CK2 inhibition induces apoptosis via the ER stress response. Cellular signalling 23:145-151.
     Hu BR, Wieloch T (1993) Casein kinase II activity in the postischemic rat brain increases in brain regions resistant to ischemia and decreases in vulnerable areas. Journal of neurochemistry 60:1722-1728.
     Hu Z, Bian X, Liu X, Zhu Y, Zhang X, Chen S, Wang K, Wang Y (2013) Honokiol protects brain against ischemia-reperfusion injury in rats through disrupting PSD95-nNOS interaction. Brain research 1491:204-212.
     Iimoto DS, Masliah E, DeTeresa R, Terry RD, Saitoh T (1990) Aberrant casein kinase II in Alzheimer`s disease. Brain research 507:273-280.
     Iyer SS, Pulskens WP, Sadler JJ, Butter LM, Teske GJ, Ulland TK, Eisenbarth SC, Florquin S, Flavell RA, Leemans JC (2009) Necrotic cells trigger a sterile inflammatory response through the Nlrp3 inflammasome. Proceedings of the National Academy of Sciences 106:20388-20393.
     Klebe R, Ruddle R (1969) Neuroblastoma-Cell culture analysis of a differentiating stem cell system. In: Journal of Cell Biology, pp A69-&: ROCKEFELLER UNIV PRESS 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021.
     Kobayashi A, Tsukide T, Miyasaka T, Morita T, Mizoroki T, Saito Y, Ihara Y, Takashima A, Noguchi N, Fukamizu A, Hirotsu Y, Ohtsuji M, Katsuoka F, Yamamoto M (2011) Central nervous system-specific deletion of transcription factor Nrf1 causes progressive motor neuronal dysfunction. Genes to cells : devoted to molecular & cellular mechanisms 16:692-703.
     Kozopas KM, Yang T, Buchan HL, Zhou P, Craig RW (1993) MCL1, a gene expressed in programmed myeloid cell differentiation, has sequence similarity to BCL2. Proceedings of the National Academy of Sciences 90:3516-3520.
     Ku TH, Lee YJ, Wang SJ, Fan CH, Tien LT (2011) Effect of honokiol on activity of GAD(65) and GAD(67) in the cortex and hippocampus of mice. Phytomedicine : international journal of phytotherapy and phytopharmacology 18:1126-1129.
     Kuwana T, Bouchier-Hayes L, Chipuk JE, Bonzon C, Sullivan BA, Green DR, Newmeyer DD (2005) BH3 domains of BH3-only proteins differentially regulate Bax-mediated mitochondrial membrane permeabilization both directly and indirectly. Molecular cell 17:525-535.
     Lecker SH, Goldberg AL, Mitch WE (2006) Protein degradation by the ubiquitin–proteasome pathway in normal and disease states. Journal of the American Society of Nephrology 17:1807-1819.
     Lee CS, Lee C, Hu T, Nguyen JM, Zhang J, Martin MV, Vawter MP, Huang EJ, Chan JY (2011) Loss of nuclear factor E2-related factor 1 in the brain leads to dysregulation of proteasome gene expression and neurodegeneration. Proceedings of the National Academy of Sciences 108:8408-8413.
     Letai A, Bassik MC, Walensky LD, Sorcinelli MD, Weiler S, Korsmeyer SJ (2002) Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics. Cancer cell 2:183-192.
     Li D, Chen XQ, Li W-J, Yang Y-H, Wang J-Z, Yu ACH (2007) Cytoglobin up-regulated by hydrogen peroxide plays a protective role in oxidative stress. Neurochemical research 32:1375-1380.
     Lin J-W, Chen J-T, Hong C-Y, Lin Y-L, Wang K-T, Yao C-J, Lai G-M, Chen R-M (2012) Honokiol traverses the blood-brain barrier and induces apoptosis of neuroblastoma cells via an intrinsic bax-mitochondrion-cytochrome c-caspase protease pathway. Neuro-oncology 14:302-314.
     Loizou JI, El-Khamisy SF, Zlatanou A, Moore DJ, Chan DW, Qin J, Sarno S, Meggio F, Pinna LA, Caldecott KW (2004) The protein kinase CK2 facilitates repair of chromosomal DNA single-strand breaks. Cell 117:17-28.
     Lou DY, Dominguez I, Toselli P, Landesman-Bollag E, O`Brien C, Seldin DC (2008) The alpha catalytic subunit of protein kinase CK2 is required for mouse embryonic development. Molecular and cellular biology 28:131-139.
     Luis Ulloa (1993) Depletion of casein kinase 11 by antisense oligonucleotide prevents neuritogenesis in neuroblastoma cells.
     Matsui N, Takahashi K, Takeichi M, Kuroshita T, Noguchi K, Yamazaki K, Tagashira H, Tsutsui K, Okada H, Kido Y (2009) Magnolol and honokiol prevent learning and memory impairment and cholinergic deficit in SAMP8 mice. Brain research 1305:108-117.
     Meggio F, PINNA LA (2003) One-thousand-and-one substrates of protein kinase CK2? The FASEB Journal 17:349-368.
     Mori M, Burgess D, Gefrides L, Foreman P, Opferman J, Korsmeyer S, Cavalheiro E, Naffah-Mazzacoratti MG, Noebels J (2004) Expression of apoptosis inhibitor protein Mcl1 linked to neuroprotection in CNS neurons. Cell Death & Differentiation 11:1223-1233.
     Narayanan K, Ramachandran A, Peterson MC, Hao J, Kolstø A-B, Friedman AD, George A (2004) The CCAAT enhancer-binding protein (C/EBP) β and Nrf1 interact to regulate dentin sialophosphoprotein (DSPP) gene expression during odontoblast differentiation. Journal of Biological Chemistry 279:45423-45432.
     Nencioni A, Hua F, Dillon CP, Yokoo R, Scheiermann C, Cardone MH, Barbieri E, Rocco I, Garuti A, Wesselborg S (2005) Evidence for a protective role of Mcl-1 in proteasome inhibitor-induced apoptosis. Blood 105:3255-3262.
     Nijhawan D, Fang M, Traer E, Zhong Q, Gao W, Du F, Wang X (2003) Elimination of Mcl-1 is required for the initiation of apoptosis following ultraviolet irradiation. Genes & development 17:1475-1486.
     Nikolai L. Chepelev JDB, Ting Huang, Skye McBride, William G. Willmore (2011) The Nrf1 CNC-bZIP Protein Is Regulated by the
     Proteasome and Activated by Hypoxia.
     Okoumassoun LE, Russo C, Denizeau F, Averill‐Bates D, Henderson D, Janet E (2007) Parathyroid hormone‐related protein (PTHrP) inhibits mitochondrial‐dependent apoptosis through CK2. Journal of cellular physiology 212:591-599.
     Opferman JT, Letai A, Beard C, Sorcinelli MD, Ong CC, Korsmeyer SJ (2003) Development and maintenance of B and T lymphocytes requires antiapoptotic MCL-1. Nature 426:671-676.
     Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinatesAcademic Press. New York:55-60.
     Pepperkok R, Lorenz P, Jakobi R, Ansorge W, Pyerin W (1991) Cell growth stimulation by EGF: inhibition through antisense-oligodeoxynucleotides demonstrates important role of casein kinase II. Experimental cell research 197:245-253.
     Perciavalle RM, Stewart DP, Koss B, Lynch J, Milasta S, Bathina M, Temirov J, Cleland MM, Pelletier S, Schuetz JD (2012) Anti-apoptotic MCL-1 localizes to the mitochondrial matrix and couples mitochondrial fusion to respiration. Nature cell biology 14:575-583.
     Pi J, Bai Y, Reece JM, Williams J, Liu D, Freeman ML, Fahl WE, Shugar D, Liu J, Qu W (2007) Molecular mechanism of human Nrf2 activation and degradation: role of sequential phosphorylation by protein kinase CK2. Free Radical Biology and Medicine 42:1797-1806.
     Pinna LA (1990) Casein kinase 2: an ‘eminence grise’in cellular regulation? Biochimica et Biophysica Acta (BBA)-Molecular Cell Research 1054:267-284.
     Préville X, Gaestel M, Arrigo A-P (1998) Phosphorylation is not essential for protection of L929 cells by Hsp25 against H2O2-mediated disruption actin cytoskeleton, a protection which appears related to the redox change mediated by Hsp25. Cell stress & chaperones 3:177.
     Qu WM, Yue XF, Sun Y, Fan K, Chen CR, Hou YP, Urade Y, Huang ZL (2012) Honokiol promotes non-rapid eye movement sleep via the benzodiazepine site of the GABA(A) receptor in mice. British journal of pharmacology 167:587-598.
     Radhakrishnan SK, Lee CS, Young P, Beskow A, Chan JY, Deshaies RJ (2010) Transcription factor Nrf1 mediates the proteasome recovery pathway after proteasome inhibition in mammalian cells. Molecular cell 38:17-28.
     Rebholz H, Zhou M, Nairn AC, Greengard P, Flajolet M (2013) Selective knockout of the casein kinase 2 in d1 medium spiny neurons controls dopaminergic function. Biological psychiatry 74:113-121.
     Rinkenberger JL, Horning S, Klocke B, Roth K, Korsmeyer SJ (2000) Mcl-1 deficiency results in peri-implantation embryonic lethality. Genes & development 14:23-27.
     Romieu-Mourez R, Landesman-Bollag E, Seldin DC, Sonenshein GE (2002) Protein kinase CK2 promotes aberrant activation of nuclear factor-κB, transformed phenotype, and survival of breast cancer cells. Cancer research 62:6770-6778.
     Ruzzene M, Penzo D, Pinna L (2002) Protein kinase CK2 inhibitor 4, 5, 6, 7-tetrabromobenzotriazole (TBB) induces apoptosis and caspase-dependent degradation of haematopoietic lineage cell-specific protein 1 (HS1) in Jurkat cells. Biochem J 364:41-47.
     Salvesen GS, Dixit VM (1997) Caspases: intracellular signaling by proteolysis. Cell 91:443-446.
     Satoh T, Harada N, Hosoya T, Tohyama K, Yamamoto M, Itoh K (2009) Keap1/Nrf2 system regulates neuronal survival as revealed through study of< i> keap1 gene-knockout mice. Biochemical and biophysical research communications 380:298-302.
     Schultz MA, Abdel-Mageed AB, Mondal D (2010) The Nrf1 and Nrf2 balance in oxidative stress regulation and androgen signaling in prostate cancer cells. Cancers 2:1354-1378.
     Semplici F, Meggio F, Pinna LA, Oliviero S (2002) CK2-dependent phosphorylation of the E2 ubiquitin conjugating enzyme UBC3B induces its interaction with b-TrCP and enhances b-catenin degradation. Oncogene 21:3978-3987.
     Shi Y (2006) Mechanical aspects of apoptosome assembly. Current opinion in cell biology 18:677-684.
     Srinivasula SM, Hegde R, Saleh A, Datta P, Shiozaki E, Chai J, Lee R-A, Robbins PD, Fernandes-Alnemri T, Shi Y (2001) A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis. Nature 410:112-116.
     Tang X, Yao K, Zhang L, Yang Y, Yao H (2011) Honokiol inhibits H(2)O(2)-induced apoptosis in human lens epithelial cells via inhibition of the mitogen-activated protein kinase and Akt pathways. European journal of pharmacology 650:72-78.
     Thomas LW, Lam C, Edwards SW (2010) Mcl-1; the molecular regulation of protein function. FEBS Lett 584:2981-2989.
     Tilly JL, Kolesnick RN (2002) Sphingolipids, apoptosis, cancer treatments and the ovary: investigating a crime against female fertility. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids 1585:135-138.
     Tsuchiya Y (2013) The Casein Kinase 2-Nrf1 Axis Controls the Clearance of
     Ubiquitinated Proteins by Regulating Proteasome Gene Expression.
     Ulery PG, Rudenko G, Nestler EJ (2006) Regulation of ΔFosB stability by phosphorylation. The Journal of neuroscience 26:5131-5142.
     Wang G, Ahmad KA, Ahmed K (2006) Role of protein kinase CK2 in the regulation of tumor necrosis factor-related apoptosis inducing ligand-induced apoptosis in prostate cancer cells. Cancer research 66:2242-2249.
     Wang W, Kwok AM, Chan JY (2007) The p65 isoform of Nrf1 is a dominant negative inhibitor of ARE-mediated transcription. The Journal of biological chemistry 282:24670-24678.
     Wang X (2001) The expanding role of mitochondria in apoptosis. Genes & development 15:2922-2933.
     Wang Y, Sun W, Du B, Miao X, Bai Y, Xin Y, Tan Y, Cui W, Liu B, Cui T (2013) Therapeutic effect of MG-132 on diabetic cardiomyopathy is associated with its suppression of proteasomal activities: roles of Nrf2 and NF-κB. American Journal of Physiology-Heart and Circulatory Physiology 304:H567-H578.
     Wei MC, Zong W-X, Cheng EH-Y, Lindsten T, Panoutsakopoulou V, Ross AJ, Roth KA, MacGregor GR, Thompson CB, Korsmeyer SJ (2001) Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 292:727-730.
     Willis SN, Fletcher JI, Kaufmann T, van Delft MF, Chen L, Czabotar PE, Ierino H, Lee EF, Fairlie WD, Bouillet P (2007) Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak. Science 315:856-859.
     Woodbury A, Yu SP, Wei L, Garcia P (2013) Neuro-modulating effects of honokiol: a review. Frontiers in neurology 4:130.
     Xu X, Toselli PA, Russell LD, Seldin DC (1999) Globozoospermia in mice lacking the casein kinase II α′ catalytic subunit. Nature genetics 23:118-121.
     Yang E, Zha J, Jockel J, Boise LH, Thompson CB, Korsmeyer SJ (1995) Bad, a heterodimeric partner for Bcl-x< sub> L and Bcl-2, displaces bax and promotes cell death. Cell 80:285-291.
     Yin X-M, Wang K, Gross A, Zhao Y, Zinkel S, Klocke B, Roth KA, Korsmeyer SJ (1999) Bid-deficient mice are resistant to Fas-induced hepatocellular apoptosis. Nature 400:886-891.
     Youle RJ (2007) Cellular demolition and the rules of engagement. Science 315:776-777.
     Zhai H, Nakade K, Oda M, Mitsumoto Y, Akagi M, Sakurai J, Fukuyama Y (2005) Honokiol-induced neurite outgrowth promotion depends on activation of extracellular signal-regulated kinases (ERK1/2). European journal of pharmacology 516:112-117.
     Zhang J, D`Ercole AJ (2004) Expression of Mcl-1 in cerebellar granule neurons is regulated by IGF-I in a developmentally specific fashion. Developmental brain research 152:255-263.
     Zhang P, Liu X, Zhu Y, Chen S, Zhou D, Wang Y (2013) Honokiol inhibits the inflammatory reaction during cerebral ischemia reperfusion by suppressing NF-κB activation and cytokine production of glial cells. Neuroscience letters 534:123-127.
     Zhang Y, Lucocq JM, Hayes JD (2009a) The Nrf1 CNC/bZIP protein is a nuclear envelope-bound transcription factor that is activated by t-butyl hydroquinone but not by endoplasmic reticulum stressors. The Biochemical journal 418:293-310.
     Zhang Y, Lucocq J, Hayes J (2009b) The Nrf1 CNC/bZIP protein is a nuclear envelope-bound transcription factor that is activated by t-butyl hydroquinone but not by endoplasmic reticulum stressors. Biochem J 418:293-310.
     Zhang Y, Lucocq J, Yamamoto M, Hayes J (2007) The NHB1 (N-terminal homology box 1) sequence in transcription factor Nrf1 is required to anchor it to the endoplasmic reticulum and also to enable its asparagine-glycosylation. Biochem J 408:161-172.		zh_TW