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姓名	田子函(Zi-Han Tian)  查詢紙本館藏	畢業系所	生命科學系
論文名稱	檳榔生物鹼調節3T3-L1前脂肪細胞的生長 (Betel nut alkaloids regulate 3T3-L1 preadipocyte growth)
相關論文	★ 中華鱉腦垂體甘丙氨激素之研究：cDNA選殖、表現及調控 ★ 辛基苯酚對3T3-L1脂肪細胞中resistin的調節作用 ★ 綠茶表沒食子酸酯型唲茶素酸酯對胰島素刺激前脂肪細胞增生的抑制 ★ FoxO1 調節抗胰島素激素基因的表現 ★ 綠茶表沒食子唲茶素沒食子酸酯受器對於人類乳癌細胞株MCF7生長的影響 ★ 綠茶表沒食子酸酯型唲茶素酸酯抑制第一型内皮素作用於脂肪細胞上攝入葡萄糖的訊息機制 ★ 綠茶表兒茶素藉由microRNA-494路徑改善橫向主動脈繃紮術誘導型小鼠的心臟疾病 ★ 內皮素誘導前脂肪細胞生長的訊息路徑 ★ 綠茶對前脂肪細胞生長的影響 ★ 綠茶唲茶素對由第一型類胰島素所調節前脂肪細胞生長的影響 ★ 綠茶唲茶素對於前脂肪細胞分化的影響 ★ Cdk2在綠茶唲茶素調節3T3-L1前脂肪細胞的生長和細胞凋亡扮演著必要性的角色 ★ 綠茶唲茶素透過MAPK相關途徑抑制3T3-L1前脂肪細胞的生長 ★ 第一型類胰島素生長因子、綠茶唲茶素及雌性素對3T3-L1脂肪細胞中resistin的基因表達有不同的調節效果 ★ 綠茶唲茶素對前脂肪細胞內活性氧及榖胱甘肽的影響 ★ 胰島素接受器受質在綠茶唲茶素對胰島素刺激前脂肪細胞生長作用中扮演的角色
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摘要(中)	檳榔是亞洲最廣泛消費的物質之一，其檳榔生物鹼（Betal nut alkaloids），尤其是檳榔鹼(arecoline)，被發現存在於檳榔嚼食者的唾液。雖然檳榔鹼已被證實在3T3-L1脂肪細胞會調節葡萄糖攝取和脂肪生成，但檳榔鹼對前脂肪細胞生長的作用之相關訊息是很少的。利用3T3-L1前脂肪細胞，我們觀察到檳榔鹼，但不包括其他結構上相似的生物鹼，如arecaidine和guvacine，對3T3-L1前脂肪細胞會劑量依賴性和時間依賴性地降低細胞生存率。流式細胞儀分析細胞週期的變化後顯示，處理檳榔鹼但並非arecaidine或guvacine， 24和48小時3T3-L1前脂肪細胞的細胞群體分佈中，G1期會減少並且增加S期和G2 / M期。進一步的西方點墨法分析結果顯示，檳榔鹼在24小時使G1檢查點刺激蛋白質總量降低，如p21，p27和AMP活化蛋白激酶（AMP-activated protein kinase）的蛋白質總量，並減少了G2檢查點調控蛋白的總量如CDK1，增加細胞週期素(cyclin) B1和p53的含量，但沒有改變CDK2蛋白總量。有趣的是，arecaidine和guvacine改變p21和p53的蛋白總量但不改變p27，CDK1，CDK2和cyclin B1的蛋白總量。預處理穀胱甘肽活化劑例如N-乙酰半胱氨酸（NAC），抑制了檳榔鹼所誘導的細胞生存率之減少和細胞週期的G1期的分佈之降低。此外，NAC阻斷檳榔鹼所增加的S和G2/M期細胞分布以及活性氧（ROS）的產生。另外，預處理NAC阻止了 arecoline 所降低的p21, p27，CDK1和AMPK蛋白，和增加的p53和cyclin B1蛋白質總量。不過毒蕈鹼型乙酰膽鹼受體（muscarinic acetylcholine receptor）拮抗劑，如阿托品(atropine)，並沒有阻止檳榔鹼所降低細胞存活率，但進一步地強化檳榔鹼刺激ROS的產生。另外GABA及其B型受器抑制劑-saclofen皆無法抑制arecoline所降低的細胞存活率。總結，檳榔生物鹼成分中會選擇性的僅arecoline會透過ROS而非mAchR和GABA B型受器的路徑，改變p53、p21、p27、CDK1、cyclin B1及AMPK蛋白表現量，進而調控細胞週期的變化，使得3T3-L1前脂肪細胞的生長受到抑制。
摘要(英)	Betel nut is one of the common substances consumed in Asia, and betel nut alkaloids (BNAs), especially arecoline, are found to be present in the saliva of areca nut chewers. Although arecoline has been shown to regulate glucose uptake and adipogenesis in 3T3-L1 adipocytes, little information is known about the action of arecoline on growth of preadipocytes. Using 3T3-L1 preadipocytes, we observed that arecoline, but not other structurally related alkaloids, such as arecaidine or guvacine, reduced cell viability of 3T3-L1 preadipocytes in dose- and time-dependent manners. Flow cytometric analysis of the cell cycle indicated that exposure to arecoline, but not arecaidine or guvacine, for 24 and 48 h decreased the cell population in G1 stage and increased the cell population in S stage and the G2/M stage of 3T3-L1 preadipocytes. Further Western blot analysis showed that arecoline at 24 h reduced levels of the G1 checkpoint-stimulating proteins, such as p21, p27 and AMP-activated protein kinase (AMPK), decreased levels of the G2 checkpoint-controlling protein, such as CDK1, increased cyclin B1 and p53 protein level, and unaltered CDK2 protein level. Interestingly, arecaidine and guvacine altered p21 and p53 protein levels and unaltered p27, CDK1, CDK2, and cyclin B1 protein levels. Pretreatment with N-acetyl-cysteine (NAC), a glutathione activator, suppressed the arecoline-induced decreases in levels of cell viability and G1 phase of the cell cycle. Moreover, NAC blocked the arecoline-increased percentages of S and G2/M stages of the cell cycle and levels of reactive oxygen species (ROS) production. In addition, NAC prevented the arecoline-decreased levels of p21, p27, CDK1 and AMPK proteins and the arecoline-increased levels of p53 and cyclin B1. However the muscarinic acetylcholine receptor (mAChR) antagonist, such as atropine, did not block the arecoline-reduced cell viability but enhanced further arecoline-stimulated ROS production. Neither GABA nor its type B receptor antagonist, such as saclofen, blocked arecoline-suppressed cell viability. In conclusion, arecoline is the selective ingredient from BNAs to inhibit 3T3-L1 preadipocyte growth through alterations of the cell cycle possibly in p53-, p21-, p27-, CDK1-, cyclin B1, AMPK- and ROS-dependent pathways and GABA B receptor- and mAChR-independent pathways.
關鍵字(中)	★ 檳榔生物鹼 ★ 檳榔鹼 ★ 3T3-L1前脂肪細胞 ★ 細胞週期	關鍵字(英)	★ Betel nut alkaloids ★ arecoline ★ 3T3-L1 preadipocyte ★ cell cycle
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參考文獻	七、參考文獻 [1] Gupta PC, Ray CS., 2004. Epidemiology of betel quid usage. Ann Acad Med Singapore 33, 31-6. [2] Ko YC, Chiang TA, Chang SJ, Hsieh SF., 1992. Prevalence of betel quid chewing habit in Taiwan and related sociodemographic factors. J Oral Pathol Med. 21, 261-4. [3] Cox S, Vickers ER, Ghu S, Zoellner H., 2010. Salivary arecoline levels during areca nut chewing in human volunteers. J Oral Pathol Med. 39, 465-9. [4] Nair, J., Ohshima, H., Friesen, M., Croisy, A., Bhide, S. V., and Bartsch, H., 1985. Tobacco-specific and betel nut-specific N-nitroso compounds: Occurrence in saliva and urine of betel quid chewers and formation in vitro by nitrosation of betel quid. Carcinogenesis 6, 295–303. [5] IARC., 2004. Betel-quid and areca-nut chewing. IARC Monogr Eval Carcinog Risk Chem Hum 37, 137–202. [6] Giri S, Idle JR, Chen C, Zabriskie TM, Krausz KW, Gonzalez FJ., 2006. A metabolomic approach to the metabolism of the areca nut alkaloids arecoline and arecaidine in the mouse. Chem Res Toxicol. 19, 818-27. [7] Asthana S, Greig NH, Holloway HW, Raffaele KC, Berardi A, Schapiro MB, Rapoport SI, Soncrant TT., 1996. Clinical pharmacokinetics of arecoline in subjects with Alzheimer′s disease. Clin Pharmacol Ther. 60, 276-82. [8] Wenke G, Brunnemann KD, Hoffmann D, Bhide SV., 1984. A study of betel quid carcinogenesis IV. Analysis of the saliva of betel chewers: A preliminary report. J Cancer Res Clin Oncol. 108, 110-3. [9] Saikia JR, Schneeweiss FH, Sharan RN., 1999. Arecoline-induced changes of poly-ADP-ribosylation of cellular proteins and its influence on chromatin organization. Cancer Lett. 139, 59-65. [10] Jeng JH, Chang MC, Hahn LJ., 2001. Role of areca nut in betel quid-associated chemical carcinogenesis: current awareness and future perspectives. Oral Oncol. 37, 477-92. [11] Sundqvist K, Liu Y, Nair J, Bartsch H, Arvidson K, Grafström RC., 1989. Cytotoxic and genotoxic effects of areca nut-related compounds in cultured human buccal epithelial cells. Cancer Res. 49, 5294-8. [12] Jeng JH, Tsai CL, Hahn LJ, Yang PJ, Kuo YS, Kuo MY., 1999. Arecoline cytotoxicity on human oral mucosal fibroblasts related to cellular thiol and esterase activities. Food Chem Toxicol. 37, 751-6. [13] Shih YT, Chen PS, Wu CH, Tseng YT, Wu YC, Lo YC., 2010. Arecoline, a major alkaloid of the areca nut, causes neurotoxicity through enhancement of oxidative stress and suppression of the antioxidant protective system. Free Radic Biol Med. 49, 1471-9. [14] Dasgupta R, Saha I, Pal S, Bhattacharyya A, Sa G, Nag TC, Das T, Maiti BR., 2006. Immunosuppression, hepatotoxicity and depression of antioxidant status by arecoline in albino mice. Toxicology 227, 94-104. [15] Chang MC, Ho YS, Lee PH, Chan CP, Lee JJ, Hahn LJ, Wang YJ, Jeng JH., 2001. Areca nut extract and arecoline induced the cell cycle arrest but not apoptosis of cultured oral KB epithelial cells: association of glutathione, reactive oxygen species and mitochondrial membrane potential. Carcinogenesis 22, 1527-35. [16] Thangjam GS, Kondaiah P., 2009. Regulation of oxidative-stress responsive genes by arecoline in human keratinocytes. J Periodontal Res. 44, 673-82. [17] Tsai CH, Yang SF, Chen YJ, Chu SC, Hsieh YS, Chang YC., 2004. Regulation of interleukin-6 expression by arecoline in human buccal mucosal fibroblasts is related to intracellular glutathione levels. Oral Dis. 10, 360-4. [18] Rajeshwar N. Sharan mail, Ravi Mehrotra, Yashmin Choudhury, Kamlesh Asotra, 2012. Association of betel nut with carcinogenesis: Revisit with a clinical perspective. PLoS One 7, 1-21. [19] Lai YL, Lin JC, Yang SF, Liu TY, Hung SL., 2007. Areca nut extracts reduce the intracellular reactive oxygen species and release of myeloperoxidase by human polymorphonuclear leukocytes. J Periodontal Res. 42, 69-76. [20] Lanzafame AA, Christopoulos A, Mitchelson F., 2003. Cellular signaling mechanisms for muscarinic acetylcholine receptors. Receptors Channels 9, 241-60. [21] Ghelardini C, Galeotti N, Lelli C, Bartolini A., 2001. M1 receptor activation is a requirement for arecoline analgesia. Farmaco. 56, 383-5. [22] Yang YR, Chang KC, Chen CL, Chiu TH., 2000. Arecoline excites rat locus coeruleus neurons by activating the M2-muscarinic receptor. Chin J Physiol. 43, 23-8. [23] Xie DP, Chen LB, Liu CY, Zhang CL, Liu KJ, Wang PS., 2004. Arecoline excites the colonic smooth muscle motility via M3 receptor in rabbits. Chin J Physiol. 47, 89-94. [24] Chiu CC, Chen BH, Hour TC, Chiang WF, Wu YJ, Chen CY, Chen HR, Chan PT, Liu SY, Chen JY., 2010. Betel quid extract promotes oral cancer cell migration by activating a muscarinic M4 receptor-mediated signaling cascade involving SFKs and ERK1/2. Biochem Biophys Res Commun. 399, 60-5. [25] Chu NS., 2001. Effects of betel chewing on the central and autonomic nervous systems. J Biomed Sci. 8, 229-36. [26] Tillakaratne NJ, Medina-Kauwe L, Gibson KM., 1995. Gamma-aminobutyric acid (GABA) metabolism in mammalian neural and non-neural tissues. Comp Biochem Physiol A Physiol. 112, 247-63. [27] Tillakaratne NJ, Medina-Kauwe L, Gibson KM., 1995. Gamma-aminobutyric acid (GABA) metabolism in mammalian neural and non-neural tissues. Comp Biochem Physiol A Physiol. 112, 247-63. [28] Lodge D, Johnston GA, Curtis DR, Brand SJ., 1977. Effects of the Areca nut constituents arecaidine and guvacine on the action of GABA in the cat central nervous system. Brain Res. 136, 513-22. [29] Chempakam B., 1993. Hypoglycaemic activity of arecoline in betel nut Areca catechu. Indian J Exp Biol. 31, 474-5. [30] Peungvicha P, Thirawarapan SS, Temsiririrkkul R, Watanabe H, Kumar Prasain J, Kadota S., 1998. Hypoglycaemic effect of Bthe water extract of Piper sarmentosum in rats. J Ethnopharmacol. 60, 27-32. [31] Sorenson RL, Garry DG, Brelje TC., 1991. Structural and functional considerations of GABA in Islets of Langerhans. Beta-cells and nerves. Diabetes 40, 1365-74. [32] Martino GV, Tappaz ML, Braghi S, Dozio N, Canal N, Pozza G, Bottazzo GF, Grimaldi LM, Bosi E., 1991. Autoantibodies to glutamic acid decarboxylase (GAD) detected by an immuno-trapping enzyme activity assay: relation to insulin-dependent diabetes mellitus and islet cell antibodies. J Autoimmun. 4, 915-23. [33] Rajesh N. Sharan, Yashmin C, 2010. Betel Nut and Susceptibility to Cancer. Environmental Factors, Genes, and the Development of Human Cancers 401-428. [34] Chiang CP, Chang MC, Lee JJ, Chang JY, Lee PH, Hahn LJ, Jeng JH., 2004. Hamsters chewing betel quid or areca nut directly show a decrease in body weight and survival rates with concomitant epithelial hyperplasia of cheek pouch. Oral Oncol. 40,720-7. [35] Kumpawat K, Deb S, Ray S, Chatterjee A., 2003. Genotoxic effect of raw betel-nut extract in relation to endogenous glutathione levels and its mechanism of action in mammalian cells. Mutat Res. 538, 1-12. [36] Wary KK, Sharan RN., 1988. Aqueous extract of betel-nut of North-East India induces DNA strand breaks and enhances rate of cell proliferation in vitro. J Cancer Res Clin Oncol. 114, 579-82. [37] Hung SL, Cheng YY, Peng JL, Chang LY, Liu TY, Chen YT., 2005. Inhibitory effects of areca nut extracts on phagocytosis of actinobacillus actinomycetemcomitans ATCC 33384 by neutrophils. J Periodontol. 76, 373-9. [38] Hsu HJ, Chang KL, Yang YH, Shieh TY., 2001. The effects of arecoline on the release of cytokines using cultured peripheral blood mononuclear cells from patients with oral mucous diseases. Kaohsiung J Med Sci. 17,175-82. [39] Liu TY, Chen CL, Chi CW., 1996. Oxidative damage to DNA induced by areca nut extract. Mutat Res. 367, 25-31. [40] Chang WC, Hsiao CF, Chang HY, Lan TY, Hsiung CA, Shih YT, Tai TY., 2006. Betel nut chewing and other risk factors associated with obesity among Taiwanese male adults. Int J Obes (Lond). 30, 359-63. [41] Guh Jinn-Yuh, Chuang Lea-Yea, and Chen Hung-Chun, 2006. Betel-quid use is associated with the risk of the metabolic syndrome in adults. Am J Clin Nutr. 83, 61313-1320. [42] Yen AM, Chiu YH, Chen LS, Wu HM, Huang CC, Boucher BJ, Chen TH., 2006. A population-based study of the association between betel-quid chewing and the metabolic syndrome in men. Am J Clin Nutr. 83, 1153-60. [43] JOHN M. STOWERS, STANLEY B., W. Ewen., 1991. Possible dietary factors in the induction of diabetes and its inheritance in man, with studies in mice. Proceedings of the Nutrition Society 50, 287-298. [44] Boucher BJ, Ewen SW, Stowers JM., 1994. Betel nut (Areca catechu) consumption and the induction of glucose intolerance in adult CD1 mice and in their F1 and F2 offspring. Diabetologia 37, 49-55. [45] Boucher BJ, Mannan N., 2002. Metabolic effects of the consumption of Areca catechu. Addict Biol. 7, 103-10. [46] Hsu HF, Tsou TC, Chao HR, Shy CG, Kuo YT, Tsai FY, Yeh SC, Ko YC., 2010. Effects of arecoline on adipogenesis, lipolysis, and glucose uptake of adipocytes—A possible role of betel-quid chewing in metabolic syndrome. Toxicol Appl Pharmacol. 245, 370-7. [47] Hsieh TJ, Hsieh PC, Wu MT, Chang WC, Hsiao PJ, Lin KD, Chou PC, Shin SJ., 2011. Betel nut extract and arecoline block insulin signaling and lipid storage in 3T3-L1 adipocytes. Cell Biol Toxicol. 27, 397-411. [48] Ku HC, Liu HS, Hung PF, Chen CL, Liu HC, Chang HH, Tsuei YW, Shih LJ, Lin CL, Lin CM, Kao YH., 2012. Green tea (–)-epigallocatechin gallate inhibits IGF-I and IGF-IIstimulation of 3T3-L1 preadipocyte mitogenesis via the 67-kDa laminin receptor, but not AMP-activated protein kinase pathway. Mol Nutr Food Res. 56, 580-92. [49] Hung TC, Huang LW, Su SJ, Hsieh BS, Cheng HL, Hu YC, Chen YH, Hwang CC, Chang KL., 2011. Hemeoxygenase-1 expression in response to arecoline-induced oxidative stress in human umbilical vein endothelial cells. Int J Cardiol. 151, 187-94. [50] Ho WH, Lee YY, Chang LY, Chen YT, Liu TY, Hung SL., 2010. Effects of areca nut extract on the apoptosis pathways in human neutrophils. J Periodontal Res. 45, 412-20. [51] Chou WW, Guh JY, Tsai JF, Hwang CC, Chen HC, Huang JS, Yang YL, Hung WC, Chuang LY., 2008. Arecoline-induced growth arrest and p21WAF1 expression are dependent on p53 in rat hepatocytes. Toxicology 243, 1-10. [52] Huang LW, Hsieh BS, Cheng HL, Hu YC, Chang WT, Chang KL., 2012. Arecoline decreases interleukin-6 production and induces apoptosis and cell cycle arrest in human basal cell carcinoma cells. Toxicol Appl Pharmacol. 258, 199-207. [53] Tseng SK, Chang MC, Su CY, Chi LY, Chang JZ, Tseng WY, Yeung SY, Hsu ML, Jeng JH., 2012. Arecoline induced cell cycle arrest, apoptosis, and cytotoxicity to human endothelial cells. Clin Oral Investig. 16, 1267-73. [54] Tsai YS, Lee KW, Huang JL, Liu YS, Juo SH, Kuo WR, Chang JG, Lin CS, Jong YJ., 2008. Arecoline, a major alkaloid of areca nut, inhibits p53, represses DNA repair, and triggers DNA damage response in human epithelial cells. Toxicology 249, 230-7. [55] Chang YC, Hu CC, Lii CK, Tai KW, Yang SH, Chou MY., 2001. Cytotoxicity and arecoline mechanisms in human gingival fibroblasts in vitro. Clin Oral Investig. 5, 51-6. [56] Yen CY, Lin MH, Liu SY, Chiang WF, Hsieh WF, Cheng YC, Hsu KC, Liu YC., 2011. Arecoline-mediated inhibition of AMP-activated protein kinase through reactive oxygen species is required for apoptosis induction. Oral Oncol. 47, 345-51. [57] Zafarullah M, Li WQ, Sylvester J, Ahmad M., 2003. Molecular mechanisms of N-acetylcysteine actions. Cell Mol Life Sci. 60, 6-20. [58] Arredondo J, Hall LL, Ndoye A, Chernyavsky AI, Jolkovsky DL, Grando SA., 2003. Muscarinic acetylcholine receptors regulating cell cycle progression are expressed in human gingival keratinocytes. J Periodontal Res. 38, 79-89. [59] Lee PH, Chang MC, Chang WH, Wang TM, Wang YJ, Hahn LJ, Ho YS, Lin CY, Jeng JH., 2006. Prolonged exposure to arecoline arrested human KB epithelial cell growth: Regulatory mechanisms of cell cycle and apoptosis. Toxicology 220, 81-9. [60] Kuo FC, Wu DC, Yuan SS, Hsiao KM, Wang YY, Yang YC, Lo YC., 2005. Effects of arecoline in relaxing human umbilical vessels and inhibiting endothelial cell growth. J Perinat Med. 33, 399-405. [61] Chang YC, Hu CC, Lii CK, Tai KW, Yang SH, Chou MY., 2001. Cytotoxicity and arecoline mechanisms in human gingival fibroblasts in vitro. Clin Oral Investig. 5, 51-6. [62] Ji WT, Yang SR, Chen JY, Cheng YP, Lee YR, Chiang MK, Chen HR., 2012. Arecoline downregulates levels of p21 and p27 through the reactive oxygen species/mTOR complex 1 pathway and may contribute to oral squamous cell carcinoma. Cancer Sci. 103, 1221-9. [63] Ling YH, Consoli U, Tornos C, Andreeff M, Perez-Soler R., 1998. Accumulation of cyclin B1, activation of cyclin B1-dependent kinase and induction of programmed cell death in human epidermoid carcinoma KB cells treated with taxol. Int J Cancer. 75, 925-32. [64] Li JM, Brooks G., 1999. Cell cycle regulatory molecules (cyclins, cyclin-dependent kinases and cyclin-dependent kinase inhibitors) and the cardiovascular system: potential targets for therapy? Eur Heart J. 20, 406-20. [65] Meister A, Anderson ME., 1983. Glutathione. Annu Rev Biochem. 52, 711-60. [66] Shackelford RE, Kaufmann WK, Paules RS., 2000. Oxidative stress and cell cycle checkpoint function. Free Radic Biol Med. 28, 1387-404. [67] Dickinson DA, Forman HJ., 2002. Cellular glutathione and thiols metabolism. Biochem Pharmacol. 64, 1019-26. [68] Rahman I, MacNee W., 2000. Regulation of redox glutathione levels and gene transcription in lung inflammation: therapeutic approaches. Free Radic Biol Med. 28, 1405-20. [69] Wess J, Lambrecht G, Moser U, Mutschler E., 1987. Stimulation of ganglionic muscarinic M1 receptors by a series of tertiary arecaidine and isoarecaidine esters in the pithed rat. Eur J Pharmacol. 134, 61-7. [70] IARC. Other Data Relevant to an Evaluation of carcinogenicity and its mechanisms. IARC MONOGRAPHS 85, 160-230. [71] Stephens M, Rees D, Ludgate M., 2009. Muscarinic acetylcholine receptors and adipogenesis. Endocrine Abstracts 19, 129. [72] Yang TT, Chang CK, Tsao CW, Hsu YM, Hsu CT, Cheng JT., 2009. Activation of muscarinic M-3 receptor may decrease glucose uptake and lipolysis in adipose tissue of rats. Neurosci Lett. 451, 57-9. [73] Yukari N, Eiichi H, Takeshi T, Yoshifumi T, Tomomi Y, Hiroyuki F, Saya T, Syota H, Yukio Y, 2011. Positive regulation by GABABR1 subunit of leptin expression through gene transactivation in adipocytes. PLoS ONE 6, e20167. [74] 鄭靖耀，「檳榔生物鹼對於前列腺癌細胞生長和轉移的影響」，國立中央大學，碩士論文，民國103年。 [75] Habinowski SA, Witters LA., 2001. The effects of AICAR on adipocyte differentiation of 3T3-L1 cells. Biochem Biophys Res Commun. 286, 852-6. [76] Chou WW1, Guh JY, Tsai JF, Hwang CC, Chiou SJ, Chuang LY., 2009. Arecoline-induced phosphorylated p53 and p21(WAF1) protein expression is dependent on ATM/ATR and phosphatidylinositol-3-kinase in clone-9 cells. J Cell Biochem. 107, 408-17. [77] Taylor WR, Stark GR., 2001. Regulation of the G2/M transition by p53. Oncogene. 20, 1803-15. [78] Watanabe M, Maemura K, Oki K, Shiraishi N, Shibayama Y, Katsu K., 2006. Gamma-aminobutyric acid (GABA) and cell proliferation: focus on cancer cells. Histol Histopathol. 21, 1135-41. [79] Bringmann A, Grosche A, Pannicke T, Reichenbach A., 2013. GABA and Glutamate Uptake and Metabolism in Retinal Glial (Müller) Cells. Front Endocrinol (Lausanne). 4, 48.
指導教授	高永旭(Yung-Hsi Kao)	審核日期	2014-10-22
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