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研究生:曾曉玲
研究生(外文):Hsiao-Ling Tseng
論文名稱:探討Quercetin-3-O-methyl ether對Cu2+誘發肝臟氧化壓力之保護機制
論文名稱(外文):Investigation of hepatoprotective mechanism on Cu2+-induced oxidative stress by quercetin-3-O-methyl ether
指導教授:徐雪瑩
指導教授(外文):Hsue-Yin Hsu
學位類別:碩士
校院名稱:慈濟大學
系所名稱:生命科學系碩士班
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:2011
畢業學年度:99
語文別:中文
論文頁數:60
中文關鍵詞:氧化壓力氧化還原平衡
外文關鍵詞:oxidative stressredox homeostasis
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類黃酮(flavonoid)為多酚類(polyphenolic)化合物的主要組成,存在植物中使之具有多項生物活性。槲皮素(quercetin)是類黃酮中最常用以研究生物活性的成分,已知槲皮素可有效抑制腫瘤細胞的侵入以及誘導細胞凋亡。Quercetin 3-O-methyl ether (Q3)是由美洲合歡所純化出具有明顯抗氧化活性的化合物,目前有關Q3的詳細調控機制仍有待釐清。本研究分別以測定細胞存活率、線粒體膜電位變化、活性氧(ROS)之產生與流式細胞儀進行銅所造成正常肝臟細胞病理生理影響之評估。活性氧在細胞之氧化壓力中可能因調節不同的訊息傳遞途徑,如PI3K/Akt和包括ERK、JNK和p38等MAPK訊息路徑,而扮演重要的角色。細胞氧化壓力增加時,粒線體膜電位之改變,連結Bad及其下游caspase 9/3的活化,將導致細胞之凋亡。本研究結果顯示,中等的銅劑量所誘導之細胞死亡,可藉由Q3使之部份恢復;而Q3保護肝臟細胞減輕銅所造成之傷害,是藉由降低14-3-3及FoxO3a蛋白所致。在銅合併Q3同時處理細胞的情形下,磷酸化Akt表現量也大幅增加,因此推測PI3K/Akt路徑參與調節的訊息傳遞過程;細胞活性氧的含量變化,證實Q3可能具有保護細胞不受銅所誘發之氧化壓力傷害的能力。為了進一步以細胞生物學角度探討Q3對銅所誘發肝臟傷害的保護功能,本研究也以轉殖基因斑馬魚Tg (LFABP-EGFP)作為實驗動物模式,研究Q3對於銅所造成肝臟損傷之保護作用。體內研究所得與細胞體外之研究結果相同,顯示Q3具有降低銅所造成氧化傷害並保護斑馬魚胚胎及成魚肝臟之功能。
Flavonoids are abundant plants polyphenolic compounds that display several biological activities. Quercetin is one of the best-studied bioflavonoids and is known to inhibit cancer cell invasion and induce apoptosis. Quercetin 3-O-methyl ether (Q3), isolated from Calliandra haematocephala Hassk, was reported to have significant antioxidative activity. However, the detailed regulatory mechanism of Q3 is not clarified yet and still needed to be explored. In this study, the pathophysiological effect of copper on mouse normal hepatocytes cells, FL83B, was evaluated individually by determining cell viability, mitochondrial membrane potential and ROS generation by flow cytometry. ROS may play an important role in regulating different signal transduction pathways in the cells such as PI3K/Akt and MAPK pathway that ERK, JNK and p38 are included. Changes of mitochondrial membrane potential as caused by increased oxidative stress and reciprocal regulation of Bad in association with activation of caspase 9/3 were known to lead ultimately to apoptotic cell death. Our results show that the significant cell death induced by a moderate copper dose could be partially recovered by Q3 and the protection of Q3 on FL83B cells was found to modulate the copper-induced cell death by downregulation of 14-3-3 and FoxO3a. The elevated phosphorylation of Akt in FL83B cells cotreated by copper and Q3 indicated that PI3K/Akt could be involved in the regulatory pathway. Changes of cellular ROS indicated that Q3 might have the potential to protect cells from oxidative stress induced by Cu2+. To further investigate the in vivo effects of Q3 on preventing hepatic damages induced by Cu2+, the zebrafish Tg (LFABP-EGFP) was used as a model organism in this study. Consisdent with the observations from treatments in vitro, Q3 was also shown to protect the liver of both embryonic and adult zebrafish from Cu2+-induced oxidative damages.
Abstract................................................................1
中文摘要................................................................3
前言....................................................................4
一、肝臟與其病變........................................................4
二、自由基及活性氧之定義................................................4
三、金屬離子之氧化傷害..................................................5
四、細胞凋亡(cell apoptosis)............................................6
五、Akt訊息傳遞路徑.....................................................7
六、FoxO轉錄因子調控....................................................7
七、Akt與FoxO之調控關係.................................................8
八、MAPK訊息傳遞路徑....................................................9
九、細胞之抗氧化防禦機制...............................................10
十、細胞內之抗氧化物質.................................................10
研究動機與目標.........................................................14
材料與方法.............................................................15
細胞培養 (Cell Culture)................................................15
細胞存活率分析 (MTT assay).............................................15
DNA 片段化分析 (DNA fragmentation analysis)............................16
螢光顯微觀察(Fluorescence microscopyic observations)...................16
流式細胞儀分析 (Flow cytometry analysis)...............................17
蛋白質萃取(Protein extraction).........................................17
西方墨點法 (Western blot)..............................................17
斑馬魚之飼養...........................................................18
Genomic DNA萃取 (Genomic DNA extraction)...............................19
聚合鏈酶反應(PCR analysis).............................................20
統計與數據分析(Biostatistics and data analysis)........................20
結果...................................................................21
Cu2+與Q3對肝臟細胞及肝癌細胞的影響.....................................21
Cu2+與Q3誘發肝臟細胞的凋亡現象.........................................22
Cu2+與Q3誘發肝臟細胞粒線體膜電位的改變.................................22
Cu2+與Q3誘發肝臟細胞凋亡的蛋白質表現分析...............................22
Cu2+與Q3對肝臟細胞ROS及GSH之影響.......................................23
Cu2+與Q3調控肝臟細胞之訊息傳遞機制:MAPK路徑...........................24
Cu2+與Q3調控肝臟細胞之訊息傳遞機制:Akt路徑............................24
Q3對Cu2+引發肝毒性影響之活體試驗.......................................25
Q3對Cu2+誘發幼魚(embryonic zebrafish)肝損傷之影響......................25
Q3對Cu2+誘發成魚肝損傷之影響...........................................26
討論...................................................................27
ROS造成細胞粒線體的傷害................................................27
Cu2+誘發ROS,導致細胞凋亡..............................................27
ROS調控MAPK之訊息傳遞路徑..............................................28
Q3促使細胞啟動防禦機制.................................................29
調控AKT傳遞路徑以及下游調控因子Bad、FoxO3a與14-3-3的相關性.............29
促使PARP進行DNA之修補..................................................30
斑馬魚模式生物.........................................................31
結論...................................................................32
參考文獻...............................................................33
Figure 1. Cu2+對肝臟細胞之影響.........................................41
Figure 2. Q3與Cu2+對肝臟細胞之影響.....................................42
Figure 3. Q3與Cu2+對肝癌細胞之影響.....................................43
Figure 4. Q3 與Cu2+對肝臟細胞影響之細胞形態觀察........................44
Figure 5. Q3與Cu2+所誘發肝臟細胞之DNA片段化............................45
Figure 6. Q3與Cu2+對肝臟細胞粒線體膜電位之影響.........................46
Figure 7. Q3對Cu2+所誘發肝臟細胞凋亡之作用.............................47
Figure 8. Q3對Cu2+引起肝臟細胞氧化壓力之影響...........................48
Figure 9. Q3對Cu2+引起肝臟細胞GSH之影響................................49
Figure 10. Q3與Cu2+對肝臟細胞MAPK路徑之調控............................50
Figure 11. Q3與Cu2+對肝臟細胞Akt路徑之調控.............................51
Figure 12. Cu2+對斑馬魚胚胎之影響......................................52
Figure 13. Cu2+對斑馬魚胚胎之肝臟傷害..................................53
Figure 14. Q3與Cu2+對斑馬魚幼魚之影響..................................54
Figure 15. Q3與Cu2+對斑馬魚幼魚肝臟螢光表現之影響......................55
Figure 16. Q3對Cu2+誘發幼魚肝毒性之影響................................56
Figure 17. Q3與Cu2+單獨或合併處理對幼魚肝臟之影響......................57
Figure 18. Q3與Cu2+單獨或合併處理對斑馬魚幼魚肝臟功能之影響............58
Figure 19. Q3與Cu2+單獨或合併處理對成魚肝臟之影響......................59
Figure 20. Q3與Cu2+單獨或合併處理對斑馬魚成魚肝臟組織之影響............60
Figure 21. Q3對Cu2+誘發肝臟細胞氧化傷害之保護機制......................61
1.Fidaleo, M., Human health risk assessment for peroxisome proliferators: more than 30 years of research. Exp Toxicol Pathol, 2009. 61(3): p. 215-21.
2.Han, Y.H., et al., Arsenic trioxide inhibits growth of As4.1 juxtaglomerular cells via cell cycle arrest and caspase-independent apoptosis. Am J Physiol Renal Physiol, 2007. 293(2): p. F511-20.
3.Gill, S.S. and N. Tuteja, Reactive oxygen species and antioxidant machinery in abiotic stress tolerance in crop plants. Plant Physiol Biochem, 2010. 48(12): p. 909-30.
4.Sato, J., et al., Effect of alcohol drinking and cigarette smoking on neutrophil functions in adults. Luminescence, 2011.
5.Mammucari, C. and R. Rizzuto, Signaling pathways in mitochondrial dysfunction and aging. Mech Ageing Dev, 2010. 131(7-8): p. 536-43.
6.Gaitanaki, C., et al., Cu2+ and acute thermal stress induce protective events via the p38-MAPK signalling pathway in the perfused Rana ridibunda heart. J Exp Biol, 2007. 210(Pt 3): p. 438-46.
7.Gaetke, L.M. and C.K. Chow, Copper toxicity, oxidative stress, and antioxidant nutrients. Toxicology, 2003. 189(1-2): p. 147-63.
8.Nicholson, D.W. and N.A. Thornberry, Caspases: killer proteases. Trends Biochem Sci, 1997. 22(8): p. 299-306.
9.Peng, T.I. and M.J. Jou, Oxidative stress caused by mitochondrial calcium overload. Ann N Y Acad Sci, 2010. 1201: p. 183-8.
10.Kitazumi, I. and M. Tsukahara, Regulation of DNA fragmentation: the role of caspases and phosphorylation. FEBS J, 2011. 278(3): p. 427-41.
11.Antonsson, B., et al., Bax oligomerization is required for channel-forming activity in liposomes and to trigger cytochrome c release from mitochondria. Biochem J, 2000. 345 Pt 2: p. 271-8.
12.Tabas, I. and D. Ron, Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nat Cell Biol, 2011. 13(3): p. 184-90.
13.Pulido, M.D. and A.R. Parrish, Metal-induced apoptosis: mechanisms. Mutat Res, 2003. 533(1-2): p. 227-41.
14.Puthalakath, H. and A. Strasser, Keeping killers on a tight leash: transcriptional and post-translational control of the pro-apoptotic activity of BH3-only proteins. Cell Death Differ, 2002. 9(5): p. 505-12.
15.Datta, S.R., et al., Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell, 1997. 91(2): p. 231-41.
16.Kane, L.P., et al., Induction of NF-kappaB by the Akt/PKB kinase. Curr Biol, 1999. 9(11): p. 601-4.
17.Lehmann, O.J., et al., Fox's in development and disease. Trends Genet, 2003. 19(6): p. 339-44.
18.Kaestner, K.H., W. Knochel, and D.E. Martinez, Unified nomenclature for the winged helix/forkhead transcription factors. Genes Dev, 2000. 14(2): p. 142-6.
19.van der Vos, K.E. and P.J. Coffer, The extending network of FOXO transcriptional target genes. Antioxid Redox Signal, 2011. 14(4): p. 579-92.
20.Barthel, A., D. Schmoll, and T.G. Unterman, FoxO proteins in insulin action and metabolism. Trends Endocrinol Metab, 2005. 16(4): p. 183-9.
21.Greer, E.L. and A. Brunet, FOXO transcription factors at the interface between longevity and tumor suppression. Oncogene, 2005. 24(50): p. 7410-25.
22.Matsuzaki, H., et al., Insulin-induced phosphorylation of FKHR (Foxo1) targets to proteasomal degradation. Proc Natl Acad Sci U S A, 2003. 100(20): p. 11285-90.
23.Kojima, T., et al., Mouse 3T3-L1 cells acquire resistance against oxidative stress as the adipocytes differentiate via the transcription factor FoxO. Apoptosis, 2010. 15(1): p. 83-93.
24.Li, M., et al., Age-related differences in insulin-like growth factor-1 receptor signaling regulates Akt/FOXO3a and ERK/Fos pathways in vascular smooth muscle cells. J Cell Physiol, 2008. 217(2): p. 377-87.
25.Moskalev, A.A., [Genetic investigations of low doze irradiation influence on life span]. Radiats Biol Radioecol, 2008. 48(2): p. 139-45.
26.Kashiwagi, A., M.J. Fein, and M. Shimada, Calpain Modulates Cyclin-Dependent Kinase Inhibitor 1B (p27(Kip1)) in Cells of the Osteoblast Lineage. Calcif Tissue Int, 2011. 89(1): p. 36-42.
27.Martinez-Gac, L., et al., Phosphoinositide 3-kinase and Forkhead, a switch for cell division. Biochem Soc Trans, 2004. 32(Pt 2): p. 360-1.
28.Huang, P., J. Han, and L. Hui, MAPK signaling in inflammation-associated cancer development. Protein Cell, 2010. 1(3): p. 218-26.
29.Johnson, G.L., Defining MAPK interactomes. ACS Chem Biol, 2011. 6(1): p. 18-20.
30.Gehart, H., et al., MAPK signalling in cellular metabolism: stress or wellness? EMBO Rep, 2010. 11(11): p. 834-40.
31.Tartaglia, M. and B.D. Gelb, Disorders of dysregulated signal traffic through the RAS-MAPK pathway: phenotypic spectrum and molecular mechanisms. Ann N Y Acad Sci, 2010. 1214: p. 99-121.
32.Shimizu, T., et al., Model mice for tissue-specific deletion of the manganese superoxide dismutase gene. Geriatr Gerontol Int, 2010. 10 Suppl 1: p. S70-9.
33.Schafer, F.Q. and G.R. Buettner, Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radic Biol Med, 2001. 30(11): p. 1191-212.
34.Hwang, C., A.J. Sinskey, and H.F. Lodish, Oxidized redox state of glutathione in the endoplasmic reticulum. Science, 1992. 257(5076): p. 1496-502.
35.Paolicchi, A., et al., Glutathione catabolism as a signaling mechanism. Biochem Pharmacol, 2002. 64(5-6): p. 1027-35.
36.Jang, J.H. and Y.J. Surh, Potentiation of cellular antioxidant capacity by Bcl-2: implications for its antiapoptotic function. Biochem Pharmacol, 2003. 66(8): p. 1371-9.
37.Dai, J., et al., Malignant cells can be sensitized to undergo growth inhibition and apoptosis by arsenic trioxide through modulation of the glutathione redox system. Blood, 1999. 93(1): p. 268-77.
38.Formica, J.V. and W. Regelson, Review of the biology of Quercetin and related bioflavonoids. Food Chem Toxicol, 1995. 33(12): p. 1061-80.
39.Schmid, H.P., et al., Nutritional aspects of primary prostate cancer prevention. Recent Results Cancer Res, 2011. 188: p. 101-7.
40.Gosslau, A., et al., The importance of natural product characterization in studies of their anti-inflammatory activity. Mol Nutr Food Res, 2011. 55(1): p. 74-82.
41.Chirumbolo, S., The role of quercetin, flavonols and flavones in modulating inflammatory cell function. Inflamm Allergy Drug Targets, 2010. 9(4): p. 263-85.
42.Chen, C., J. Zhou, and C. Ji, Quercetin: a potential drug to reverse multidrug resistance. Life Sci, 2010. 87(11-12): p. 333-8.
43.Borrelli, F. and A.A. Izzo, The plant kingdom as a source of anti-ulcer remedies. Phytother Res, 2000. 14(8): p. 581-91.
44.Ueda, Y., et al., Effects on blood pressure decrease in response to PAF of Impatiens textori MIQ. Biol Pharm Bull, 2003. 26(10): p. 1505-7.
45.Seelinger, G., I. Merfort, and C.M. Schempp, Anti-oxidant, anti-inflammatory and anti-allergic activities of luteolin. Planta Med, 2008. 74(14): p. 1667-77.
46.Kim, G.N., Y.I. Kwon, and H.D. Jang, Protective mechanism of quercetin and rutin on 2,2'-azobis(2-amidinopropane)dihydrochloride or Cu2+-induced oxidative stress in HepG2 cells. Toxicol In Vitro, 2011. 25(1): p. 138-44.
47.Kelsey, N.A., H.M. Wilkins, and D.A. Linseman, Nutraceutical antioxidants as novel neuroprotective agents. Molecules, 2010. 15(11): p. 7792-814.
48.Perez-Vizcaino, F. and J. Duarte, Flavonols and cardiovascular disease. Mol Aspects Med, 2010. 31(6): p. 478-94.
49.Huang, R.Y., et al., Immunosuppressive effect of quercetin on dendritic cell activation and function. J Immunol, 2010. 184(12): p. 6815-21.
50.Kumar, R., et al., Citrinin generated reactive oxygen species cause cell cycle arrest leading to apoptosis via the intrinsic mitochondrial pathway in mouse skin. Toxicol Sci, 2011.
51.Weng, C.J., et al., Hepatoprotection of quercetin against oxidative stress by induction of metallothionein expression through activating MAPK and PI3K pathways and enhancing Nrf2 DNA-binding activity. N Biotechnol, 2011.
52.Rubio, S., et al., Acetyl derivative of quercetin 3-methyl ether-induced cell death in human leukemia cells is amplified by the inhibition of ERK. Carcinogenesis, 2007. 28(10): p. 2105-13.
53.Tang, S.Y. and B. Halliwell, Medicinal plants and antioxidants: what do we learn from cell culture and Caenorhabditis elegans studies? Biochem Biophys Res Commun, 2010. 394(1): p. 1-5.
54.Enomoto, S., et al., Inhibitory effect of traditional Turkish folk medicines on aldose reductase (AR) and hematological activity, and on AR inhibitory activity of quercetin-3-O-methyl ether isolated from Cistus laurifolius L. Biol Pharm Bull, 2004. 27(7): p. 1140-3.
55.Moharram, F.A., et al., Antioxidant galloylated flavonol glycosides from Calliandra haematocephala. Nat Prod Res, 2006. 20(10): p. 927-34.
56.Clement, M.V. and S. Pervaiz, Reactive oxygen intermediates regulate cellular response to apoptotic stimuli: an hypothesis. Free Radic Res, 1999. 30(4): p. 247-52.
57.Thannickal, V.J. and B.L. Fanburg, Reactive oxygen species in cell signaling. Am J Physiol Lung Cell Mol Physiol, 2000. 279(6): p. L1005-28.
58.De Marco, C.S. and I. Caniggia, Mechanisms of oxygen sensing in human trophoblast cells. Placenta, 2002. 23 Suppl A: p. S58-68.
59.Cadenas, E. and K.J. Davies, Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med, 2000. 29(3-4): p. 222-30.
60.Mates, J.M. and F.M. Sanchez-Jimenez, Role of reactive oxygen species in apoptosis: implications for cancer therapy. Int J Biochem Cell Biol, 2000. 32(2): p. 157-70.
61.Linder, M.C. and M. Hazegh-Azam, Copper biochemistry and molecular biology. Am J Clin Nutr, 1996. 63(5): p. 797S-811S.
62.Handy, R.D., F.B. Eddy, and H. Baines, Sodium-dependent copper uptake across epithelia: a review of rationale with experimental evidence from gill and intestine. Biochim Biophys Acta, 2002. 1566(1-2): p. 104-15.
63.Jeon, K.I., J.Y. Jeong, and D.M. Jue, Thiol-reactive metal compounds inhibit NF-kappa B activation by blocking I kappa B kinase. J Immunol, 2000. 164(11): p. 5981-9.
64.Bremner, I., Manifestations of copper excess. Am J Clin Nutr, 1998. 67(5 Suppl): p. 1069S-1073S.
65.Wu, G.S., et al., KILLER/DR5 is a DNA damage-inducible p53-regulated death receptor gene. Nat Genet, 1997. 17(2): p. 141-3.
66.Abdelrahim, M., et al., 3,3'-diindolylmethane (DIM) and its derivatives induce apoptosis in pancreatic cancer cells through endoplasmic reticulum stress-dependent upregulation of DR5. Carcinogenesis, 2006. 27(4): p. 717-28.
67.Shenoy, K., Y. Wu, and S. Pervaiz, LY303511 enhances TRAIL sensitivity of SHEP-1 neuroblastoma cells via hydrogen peroxide-mediated mitogen-activated protein kinase activation and up-regulation of death receptors. Cancer Res, 2009. 69(5): p. 1941-50.
68.Zhuang, S. and R.G. Schnellmann, A death-promoting role for extracellular signal-regulated kinase. J Pharmacol Exp Ther, 2006. 319(3): p. 991-7.
69.Adya, R., et al., Visfatin induces human endothelial VEGF and MMP-2/9 production via MAPK and PI3K/Akt signalling pathways: novel insights into visfatin-induced angiogenesis. Cardiovasc Res, 2008. 78(2): p. 356-65.
70.Oita, R.C., et al., Visfatin induces oxidative stress in differentiated C2C12 myotubes in an Akt- and MAPK-independent, NFkB-dependent manner. Pflugers Arch, 2010. 459(4): p. 619-30.
71.Aam, B.B., O. Myhre, and F. Fonnum, Transcellular signalling pathways and TNF-alpha release involved in formation of reactive oxygen species in rat alveolar macrophages exposed to tert-butylcyclohexane. Arch Toxicol, 2003. 77(12): p. 678-84.
72.Myhre, O., et al., Erk1/2 phosphorylation and reactive oxygen species formation via nitric oxide and Akt-1/Raf-1 crosstalk in cultured rat cerebellar granule cells exposed to the organic solvent 1,2,4-trimethylcyclohexane. Toxicol Sci, 2004. 80(2): p. 296-303.
73.Steelman, L.S., et al., Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging. Aging (Albany NY), 2011. 3(3): p. 192-222.
74.Haddad, J.J., A redox microenvironment is essential for MAPK-dependent secretion of pro-inflammatory cytokines: Modulation by glutathione (GSH/GSSG) biosynthesis and equilibrium in the alveolar epithelium. Cell Immunol, 2011.
75.Bachnoff, N., M. Trus, and D. Atlas, Alleviation of oxidative stress by potent and selective thioredoxin-mimetic peptides. Free Radic Biol Med, 2011. 50(10): p. 1355-67.
76.Bartov, O., et al., Low molecular weight thiol amides attenuate MAPK activity and protect primary neurons from Abeta(1-42) toxicity. Brain Res, 2006. 1069(1): p. 198-206.
77.Sommer, S.P., et al., Glutathione preconditioning ameliorates mitochondria dysfunction during warm pulmonary ischemia-reperfusion injury. Eur J Cardiothorac Surg, 2011.
78.Kelly-Aubert, M., et al., GSH monoethyl ester rescues mitochondrial defects in cystic fibrosis models. Hum Mol Genet, 2011.
79.Ozden, O., et al., Acetylation of MnSOD directs enzymatic activity responding to cellular nutrient status or oxidative stress. Aging (Albany NY), 2011. 3(2): p. 102-7.
80.Lowes, D.A. and H.F. Galley, Mitochondrial protection by the thioredoxin-2 and glutathione systems in an in vitro endothelial model of sepsis. Biochem J, 2011. 436(1): p. 123-32.
81.Hanada, M., J. Feng, and B.A. Hemmings, Structure, regulation and function of PKB/AKT--a major therapeutic target. Biochim Biophys Acta, 2004. 1697(1-2): p. 3-16.
82.Nakae, J., M. Oki, and Y. Cao, The FoxO transcription factors and metabolic regulation. FEBS Lett, 2008. 582(1): p. 54-67.
83.Rena, G., et al., Two novel phosphorylation sites on FKHR that are critical for its nuclear exclusion. EMBO J, 2002. 21(9): p. 2263-71.
84.Kops, G.J., et al., Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress. Nature, 2002. 419(6904): p. 316-21.
85.Sundaresan, N.R., et al., Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice. J Clin Invest, 2009. 119(9): p. 2758-71.
86.Kaufmann, S.H., et al., Specific proteolytic cleavage of poly(ADP-ribose) polymerase: an early marker of chemotherapy-induced apoptosis. Cancer Res, 1993. 53(17): p. 3976-85.
87.Satoh, M.S., G.G. Poirier, and T. Lindahl, Dual function for poly(ADP-ribose) synthesis in response to DNA strand breakage. Biochemistry, 1994. 33(23): p. 7099-106.
88.Liu, Y., et al., Induction of time-dependent oxidative stress and related transcriptional effects of perfluorododecanoic acid in zebrafish liver. Aquat Toxicol, 2008. 89(4): p. 242-50.
89.Thakur, P.C., et al., Lack of De novo phosphatidylinositol synthesis leads to endoplasmic reticulum stress and hepatic steatosis in cdipt-deficient zebrafish. Hepatology, 2011.
90.North, T.E., et al., PGE2-regulated wnt signaling and N-acetylcysteine are synergistically hepatoprotective in zebrafish acetaminophen injury. Proc Natl Acad Sci U S A, 2010. 107(40): p. 17315-20.
91.Her, G.M., et al., In vivo studies of liver-type fatty acid binding protein (L-FABP) gene expression in liver of transgenic zebrafish (Danio rerio). FEBS Lett, 2003. 538(1-3): p. 125-33.
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