Thiol redox systems and protein kinases in hepatic stellate cell regulatory processes

References

• Poli G, Parola M. Oxidative damage and fibrogenesis. Free Radic Biol Med 1997;22:287–305.
   PubMed Web of Science ®Google Scholar
• Friedman SL. Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver. Physiol Rev 2008;88:125–172.
   PubMed Web of Science ®Google Scholar
• Bailey SM. A review of the role of reactive oxygen and nitrogen species in alcohol-induced mitochondrial dysfunctions. Free Radic Res 2003;37:585–596.
   PubMed Web of Science ®Google Scholar
• Atzori L, Poli G, Perra A. Hepatic stellate cell: a star cell in the liver. Int J Biochem Cell Biol 2009;41:1639–1642.
   PubMed Web of Science ®Google Scholar
• Novo E, Parola M. Redox mechanisms in hepatic chronic wound healing and fibrogenesis. Fibrogenesis Tissue Repair 2008;1:5. doi:10.1186/1755-1536-1-5.
   PubMedGoogle Scholar
• Sato M, Suzuki S, Senoo H. Hepatic stellate cells: unique characteristics in cell biology and phenotype. Cell Struct Funct 2003;28:105–112.
   PubMed Web of Science ®Google Scholar
• Blaner WS, O'Byrne SM, Wongsiriroj N, Kluwe J, D'Ambrosio DM, Jiang H, Schwabe RF, Hillman EMC, Piantedosi R, Libien J. Hepatic stellate cell lipid droplets: a specialized lipid droplet for retinoid storage. Biochim Biophys Acta 2009;1791:467–473.
   PubMed Web of Science ®Google Scholar
• Maher JJ, Bissell M, Friedman SL, Roll FJ. Collagen measured in primary cultures of normal rat hepatocytes derives from lipocytes within the monolayer. J Clin Invest 1988;82:450–459.
   PubMedGoogle Scholar
• Giampieri MP, Jezequel AM, Orlandi F. The lipocytes in normal human liver. A quantitative study. Digestion 1981;22:165–169.
   PubMedGoogle Scholar
• Hinz B, Phan SH, Thannickal VJ, Galli A, Bochaton-Piallat ML, Gabbiani G. The myofibroblast. One function, multiple origins. Am J Pathol 2007;170:1807–1816.
   PubMed Web of Science ®Google Scholar
• Nieto N, Friedman SL, Cederbaum AI. Cytochrome P450 2E1-derived reactive oxygen species mediate paracrine stimulation of collagen I protein synthesis by hepatic stellate cells. J Biol Chem 2002;277:9853–9864.
   PubMed Web of Science ®Google Scholar
• Nieto N, Friedman SL, Cederbaum AI. Stimulation and proliferation of primary rat hepatic stellate cells by cytochrome P450 2E1-derived reactive oxygen species. Hepatology 2002;35:62–73.
   PubMed Web of Science ®Google Scholar
• Canbay A, Friedman S, Gores GJ. Apoptosis: the nexus of liver injury and fibrosis. Hepatology 2004;39:273–278.
   PubMed Web of Science ®Google Scholar
• Canbay A, Higuchi H, Bronk SF, Taniai M, Sebo TJ, Gores GJ. Fas enhances fibrogenesis in the bile duct ligated mouse: a link between apoptosis and fibrosis. Gastroenterology 2002;123:1323–1330.
   PubMed Web of Science ®Google Scholar
• Canbay A, Taimr P, Torok N, Higuchi H, Friedman S, Gores GJ. Apoptotic body engulfment by a human stellate cell line is profibrogenic. Lab Invest 2003;83:655–663.
   PubMed Web of Science ®Google Scholar
• Bachem MG, Melchior R, Gressner AM. The role of thrombocytes in liver fibrogenesis: effects of platelet lysate and thrombocyte-derived growth factors on the mitogenic activity and glycosaminoglycan synthesis of cultured rat liver fat storing cells. J Clin Chem Clin Biochem 1989;27:555–565.
   PubMedGoogle Scholar
• Bilzer M, Roggel F, Gerbes AL. Role of Kupffer cells in host defense and liver disease. Liver Int 2006;26:1175–1186.
   PubMed Web of Science ®Google Scholar
• Li J-T, Liao Z-X, Ping J, Xu D, Wang H. Molecular mechanisms of hepatic stellate cell activation and antifibrotic therapeutic strategies. J Gastroenterol 2008;43:419–428.
   PubMed Web of Science ®Google Scholar
• Urtasun R, Conde de la Rosa L, Nieto N. Oxidative and nitrosative stress and fibrogenic response. Clin Liver Dis 2008;12:769–790.
   PubMed Web of Science ®Google Scholar
• Casini A, Ceni E, Salzano R, Biondi P, Parola M, Galli A, Foschi M, Caligiuri A, Pinzani M, Surrenti C. Neutrophil-derived superoxide anion induces lipid peroxidation and stimulates collagen synthesis in human hepatic cells: role of nitric oxide. Hepatology 1997;25:361–367.
   PubMed Web of Science ®Google Scholar
• Jarnagin WR, Rockey DC, Koteliansky VE, Wang SS, Bissel DM. Expression of variant fibronectins in wound healing: cellular source and biological activity of the EIIIA segment in rat hepatic fibrogenesis. J Cell Biol 1994;127:2037–2048.
   PubMed Web of Science ®Google Scholar
• Friedman SL, Wei S, Blaner WS. Retinol release by activated rat hepatic lipocytes: regulation by Kupffer cell-conditioned medium and PDGF. Am J Physiol Gastrointest Liver Physiol 1993;264:G947–G952.
   PubMedGoogle Scholar
• Pinzani M. PDGF and signal transduction in hepatic stellate cells. Front Biosc 2002;7:d1720–d1726.
   PubMedGoogle Scholar
• Pinzani M, Marra F. Cytokine receptors and signaling during stellate cell activation. Semin Liver Dis 2001;21:397–416.
   PubMed Web of Science ®Google Scholar
• Inagaki Y, Okazaki I. Emerging insights into transforming growth factor beta Smad signal in hepatic fibrogenesis. Gut 2007;56:284–292.
   PubMed Web of Science ®Google Scholar
• Arthur MJP. Fibrogenesis. II. Metalloproteinases and their inhibitors in liver fibrosis. Am J Physiol Gastrointest Liver Physiol 2000;279:G245–G249.
   PubMed Web of Science ®Google Scholar
• Iredale JP. Hepatic stellate cell behavior during resolution of liver injury. Semin Liver Dis 2001;21:427–436.
   PubMed Web of Science ®Google Scholar
• Finkel T. Redox-dependent signal transduction. FEBS Lett 2000;476:52–54.
   PubMed Web of Science ®Google Scholar
• Forman HJ, Torres M. Signaling by respiratory burst in macrophages. IUBMB Life 2001;51:365–371.
   PubMed Web of Science ®Google Scholar
• Forman HJ, Fukuto JM, Torres M. Redox signaling: thiol chemistry defines which reactive oxygen and nitrogen species can act as second messengers. Am J Physiol Cell Physiol 2004;287:C246–C256.
   PubMed Web of Science ®Google Scholar
• Forman HJ. Use and abuse of exogenous H2O2 in studies of signal transduction. Free Radic Biol Med 2007;42:926–932.
   PubMed Web of Science ®Google Scholar
• Iles KE, Dickinson DA, Watanabe N, Iwamoto T, Forman HJ. AP-1 activation through endogenous H2O2 generation by alveolar macrophages. Free Radic Biol Med 2002;32:1302–1313.
   Google Scholar
• Stone JR, Yang S. Hydrogen peroxide: a signaling messenger. Antioxid Redox Signal 2006;8:243–270.
   PubMed Web of Science ®Google Scholar
• Suzuki YJ, Forman HJ, Sevanian A. Oxidants as stimulators of signal transduction. Free Radic Biol Med 1997;22:269–285.
   PubMed Web of Science ®Google Scholar
• Meier B, Radeke HH, Selle S, Younes M, Sies H, Resch K, Habermehl GG. Human fibroblasts release reactive oxygen species in response to interleukin-1 or tumour necrosis factor-alpha. Biochem J 1989;263:539–545.
   PubMed Web of Science ®Google Scholar
• Sundaresan M, Yu Z-Y, Ferrans VJ, Irani K, Finkel T. Requirement for generation of H2O2 for platelet-derived growth factor signal transduction. Science 1995;270:296–299.
   PubMed Web of Science ®Google Scholar
• Bae YS, Kang SW, Seo MS, Baines IC, Tekle E, Chock PB, Rhee SG. Epidermal growth factor (EGF)-induced generation of hydrogen peroxide. Role in EGF receptor-mediated tyrosine phosphorylation. J Biol Chem 1997;272:217–221.
   PubMed Web of Science ®Google Scholar
• Mahadev K, Wu X, Zilbering A, Zhu L, Lawrence JTR, Goldstein BJ. Hydrogen peroxide generated during cellular insulin stimulation is integral to activation of distal insulin signaling cascade in 3T3-L1 adipocytes. J Biol Chem 2001;276:48662–48669.
   PubMedGoogle Scholar
• Carballal S, Alvarez B, Turell L, Botti H, Freeman BA, Radi R. Sulfenic acid in human serum albumin. Amino Acids 2007;32:543–551.
   PubMed Web of Science ®Google Scholar
• Moran LK, Gutteridge JMC, Quinlan GJ. Thiols in cellular redox signaling and control. Curr Med Chem 2001;8:763–772.
   PubMed Web of Science ®Google Scholar
• Schafer FQ, Buettner GR. Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radic Biol Med 2001;30:1191–1212.
   PubMed Web of Science ®Google Scholar
• Bindoli A, Fukuto JM, Forman HJ. Thiol chemistry in peroxidase catalysis and redox signaling. Antioxid Redox Signal 2008;10:1549–1564.
   PubMed Web of Science ®Google Scholar
• Li N, Ragheb K, Lawler G, Sturgis J, Rajwa B, Melendez JA, Robinson JP. Mitochondrial complex I inhibitor rotenone induces apoptosis through enhancing mitochondrial reactive oxygen species production. J Biol Chem 2003;278:8516–1525.
   PubMed Web of Science ®Google Scholar
• Pani G, Bedogni B, Colavitti R, Anzevino R, Borrello S, Galeotti T. Cell compartmentalization in redox signaling. IUBMB Life 2001;52:7–16.
   PubMedGoogle Scholar
• Ramachandran A, Moellering D, Go YM, Shiva S, Levonen AL, Jo H, Patel RP, Parthasarathy S, Darley-Usmar VM. Activation of c-Jun N-terminal kinase and apoptosis in endothelial cells mediated by endogenous generation of hydrogen peroxide. Biol Chem 2002;383:693–701.
   PubMed Web of Science ®Google Scholar
• Nemoto S, Takeda K, Yu Z-X, Ferrans VJ, Finkel T. Role for mitochondrial oxidants as regulators of cellular metabolism. Mol Cell Biol 2000;20:7311–7318.
   PubMed Web of Science ®Google Scholar
• Siegmund SV, Qian T, de Minicis S, Harvey-White J, Kunos G, Vinod KY, Hungund B, Schwabe RF. The endocannabinoid 2-arachidonoyl glycerol induces death of hepatic stellate cells via mitochondrial reactive oxygen species. FASEB J 2007;21:2798–2806.
   PubMed Web of Science ®Google Scholar
• Brookes PS, Levonen A-L, Shiva S, Sarti P, Darley-Usmar VM. Mitochondria: regulators of signal transduction by reactive oxygen and nitrogen species. Free Radic Biol Med 2002;33:755–764.
   PubMed Web of Science ®Google Scholar
• Cadenas E. Mitochondrial free radical production and cell signaling. Mol Aspects Med 2004;25:17–26.
   PubMedGoogle Scholar
• Dada LA, Chandel NS, Ridge KM, Pedemonte C, Bertorello AM, Sznajder JI. Hypoxia-induced endocytosis of Na,K-ATPase in alveolar epithelial cells is mediated by mitochondrial reactive oxygen species and PKC-ζ. J Clin Invest 2003;111:1057–1064.
   PubMed Web of Science ®Google Scholar
• Kim KH, Rodriguez AM, Carrico PM, Melendez JA. Potential mechanisms for the inhibition of tumor cell growth by manganese superoxide dismutase. Antioxid Redox Signal 2001;3:361–373.
   PubMed Web of Science ®Google Scholar
• Ranganathan AC, Nelson KK, Rodriguez AM, Kim K-H, Tower GB, Rutter JL, Brinckeroff CE, Huang T-T, Epstein CJ, Jeffrey JJ, Melendez JA. Manganese superoxide dismutase signals matrix metalloproteinase expression via H2O2-dependent ERK1/2 activation. J Biol Chem 2001;276:14264–14271.
   PubMed Web of Science ®Google Scholar
• Werner E, Werb Z. Integrins engage mitochondrial function for signal transduction by a mechanism dependent on Rho GTPases. J Cell Biol 2002;158:357–368.
   PubMed Web of Science ®Google Scholar
• Zhang DX, Gutterman DD. Mitochondrial reactive oxygen species-mediated signaling in endothelial cells. Am J Physiol Heart Circ Physiol 2007;292:H2023–H2031.
   PubMed Web of Science ®Google Scholar
• Dröge W. Free radicals in the physiological control of cell function. Physiol Rev 2002;82:47–95.
   PubMed Web of Science ®Google Scholar
• Forman HJ, Fukuto JM, Miller T, Zhang H, Rinna A, Levy S. The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal. Arch Biochem Biophys 2008;477:183–195.
   PubMed Web of Science ®Google Scholar
• Rockey DC, Chung JJ. Inducible nitric oxide synthase in rat hepatic lipocytes and the effect of nitric oxide on lipocyte contractility. J Clin Invest 1995;95:1199–1206.
   PubMedGoogle Scholar
• Halliwell B, Gutteridge JMC. Free radicals in biology and medicine. IV. Oxford: Oxford University Press; 2007.
   Google Scholar
• Holmgren A, Luthman M. Tissue distribution and subcellular localization of bovine thioredoxin determined by radioimmunoassay. Biochemistry 1978;17:4071–4077.
   PubMed Web of Science ®Google Scholar
• Dickinson DA, Forman HJ. Cellular glutathione and thiols metabolism. Biochem Pharmacol 2002;64:1019–1026.
   PubMed Web of Science ®Google Scholar
• Patwari P, Lee RT. Thioredoxins, mitochondria and hypertension. Am J Pathol 2007;170:805–808.
   PubMedGoogle Scholar
• Trotter EW, Grant CM. Non-reciprocal regulation of the redox state of the glutathione-glutaredoxin and thioredoxin systems. EMBO Rep 2003;4:184–188.
   PubMed Web of Science ®Google Scholar
• Brigelius-Flohé R. Tissue-specific functions of individual glutathione peroxidases. Free Radic Biol Med 1999;27:951–965.
   PubMed Web of Science ®Google Scholar
• Fernandes AP, Holmgren A. Glutaredoxins: glutathione-dependent redox enzymes with functions far beyond a simple thioredoxin backup system. Antioxid Redox Signal 2004;6:63–74.
   PubMed Web of Science ®Google Scholar
• Lillig CH, Holmgren A. Thioredoxin and related molecules-from biology to health and disease. Antioxid Redox Signal 2007;9:25–47.
   PubMed Web of Science ®Google Scholar
• Kanda M, Ihara Y, Murata H, Urata Y, Kono T, Yodoi J, Seto S, Yano K, Kondo T. Glutaredoxin modulates platelet-derived growth factor-dependent cell signaling by regulating the redox status of low molecular weight protein-tyrosine phosphatase. J Biol Chem 2006;281:28518–28528.
   PubMed Web of Science ®Google Scholar
• Lee SJ, Friedman SL, Whalen R, Boyer TD. Cellular sources of glutathione S-transferase P in primary cultured rat hepatocytes: localization by in situ hybridization. Biochem J 1994;299:79–83.
   PubMedGoogle Scholar
• Parola M, Pinzani M, Casini A, Leonarduzzi G, Marra F, Caligiuri A, Ceni E, Biondi P, Poli G, Dianzani MU. Induction of procollagen type I gene expression and synthesis in human hepatic stellate cells by 4-hydroxy-2,3-nonenal and other 4-hydroxy-2,3-alkenals is related to their molecular structure. Biochem Biophys Res Comm 1996;222:261–264.
   PubMedGoogle Scholar
• Whalen R, Rockey DC, Friedman SL, Boyer TD. Activation of rat hepatic stellate cells leads to loss of glutathione S-transferases and their enzymatic activity against products of oxidative stress. Hepatology 1999;30:927–933.
   PubMedGoogle Scholar
• Maher JJ, Neuschwander-Tetri BA. Manipulation of glutathione stores in rat hepatic stellate cells does not alter collagen synthesis. Hepatology 1997;26:618–623.
   PubMedGoogle Scholar
• Zamara E, Novo E, Marra F, Gentilini A, Romanelli RG, Caligiuri A, Robino G, Tamagno E, Aragno M, Danni O, Autelli R, Colombatto S, Dianzani MU, Pinzani M, Parola M. 4-hydroxynonenal as a selective pro-fibrogenic stimulus for activated human hepatic stellate cells. J Hepatol 2004;40:60–68.
   PubMed Web of Science ®Google Scholar
• de Villiers WJS, Song Z, Nasser MS, Deaciuc IV, McClain CJ. 4-hydroxynonenal-induced apoptosis in rat hepatic stellate cells: mechanistic approach. J Gastroenterol Hepatol 2007;22:414–422.
   PubMedGoogle Scholar
• Reichard JF, Vasiliou V, Petersen DR. Characterization of 4-hydroxy-2-nonenal metabolism in stellate cell lines derived from normal and cirrhotic rat liver. Biochim Biophys Acta 2000;1487:222–232.
   PubMed Web of Science ®Google Scholar
• Comporti M, Signorini C, Arezzini B, Vecchio D, Monaco B, Gardi C. Isoprostanes and hepatic fibrosis. Mol Aspects Med 2008;29:43–49.
   PubMed Web of Science ®Google Scholar
• Cubero FJ, Nieto N. Ethanol and arachidonic acid synergize to activate Kupffer cells and modulate the fibrogenic response via tumor necrosis factor α, reduced glutathione and transforming growth factor β-dependent mechanisms. Hepatology 2008;48:2027–2039.
   PubMedGoogle Scholar
• Maher JJ, Saito JM, Neuschwander-Tetri BA. Glutathione regulation in rat hepatic stellate cells. Comparative studies in primary culture and in liver injury in vivo. Biochem Pharmacol 1997;53:637–641.
   PubMedGoogle Scholar
• Zheng S, Yumei F, Chen A. De novo synthesis of glutathione is a prerequisite for curcumin to inhibit hepatic stellate cell (HSC) activation. Free Radic Biol Med 2007;43:444–453.
   PubMed Web of Science ®Google Scholar
• Fu Y, Zheng S, Lu SC, Chen A. Epigallocatechin-3-gallate inhibits growth of activated hepatic stellate cells by enhancing the capacity of glutathione synthesis. Mol Pharmacol 2008;73:1465–1473.
   PubMed Web of Science ®Google Scholar
• Bakin AV, Stourman NV, Sekhar KR, Rinehart C, Yan X, Meredith MJ, Arteaga CL, Freeman ML. Smad3-ATF3 signaling mediates TGF-β suppression of genes encoding phase II detoxifying proteins. Free Radic Biol Med 2005;38:375–387.
   PubMed Web of Science ®Google Scholar
• Kayanoki Y, Fujii J, Suzuki K, Kawata S, Matsuzawa Y, Taniguchi N. Suppression of antioxidative enzyme expresssion by transforming growth factor-β1 in rat hepatocytes. J Biol Chem 1994;269:15488–15492.
   PubMed Web of Science ®Google Scholar
• Franklin CC, Rosenfeld-Franklin ME, White C, Kavanagh TJ, Fausto N. TGF beta1-induced suppression of glutathione antioxidant defenses in hepatocytes: caspase-dependent post-translational and caspase-independent transcriptional regulatory mechanisms. FASEB J 2003;17:1535–1537.
   PubMedGoogle Scholar
• De Bleser PJ, Xu G, Rombouts K, Rogiers V, Geerts A. Glutathione levels dicriminate between oxidative stress and transforming growth factor-β signaling in activated rat hepatic stellate cells. J Biol Chem 1999;274:33881–33887.
   PubMed Web of Science ®Google Scholar
• Jameel NM, Thirunavukkarasu C, Wu T, Watkins SC, Friedman SL, Gandhi CR. p38-MAPK- and caspase-3-mediated superoxide-induced apoptosis of rat hepatic stellate cells: reversal by retinoic acid. J Cell Physiol 2009;218:157–166.
   PubMed Web of Science ®Google Scholar
• Kawada N, Kristensen DB, Asahina K, Nakatani K, Minamiyama Y, Seki S, Yoshizato K. Characterization of a stellate cell activation-associated protein (STAP) with peroxidase activity found in rat hepatic stellate cells. J Biol Chem 2001;276:25318–25323.
   PubMed Web of Science ®Google Scholar
• Nakatani K, Okuyama H, Shimahara Y, Saeki S, Kim D-Ho, Nakajima Y, Seki S, Kawada N, Yoshizato K. Cytoglobin/STAP, its unique localization in splanchnic fibroblast-like cells and function in organ fibrogenesis. Lab Invest 2004;84:91–101.
   PubMedGoogle Scholar
• Arnér ES, Holmgren A. Physiological functions of thioredoxin and thioredoxin reductase. Eur J Biochem 2000;267:6102–6109.
   PubMedGoogle Scholar
• Powis G, Briehl M, Oblong J. Redox signalling and the control of cell growth and death. Pharmacol Ther 1995;68:149–173.
   PubMed Web of Science ®Google Scholar
• Gladyshev VN, Jeang KT, Stadtman TC. Selenocysteine, identified as the penultimate C-terminal residue in human T-cell thioredoxin reductase, corresponds to TGA in the human placental gene. Proc Natl Acad Sci USA 1996;93:6146–6151.
   PubMed Web of Science ®Google Scholar
• Zhong L, Arnér ES, Ljung J, Aslund F, Holmgren A. Rat and calf thioredoxin reductase are homologous to glutathione reductase with a carboxyl-terminal elongation containing a conserved catalytically active penultimate selenocysteine residue. J Biol Chem 1998;273:8581–8591.
   PubMed Web of Science ®Google Scholar
• Lee S-R, Kim J-R, Kwon K-S, Yoon HW, Levine RL, Ginsburg A, Rhee SG. Molecular cloning and characterization of a mitochondrial selenocysteine-containing thioredoxin reductase from rat liver. J Biol Chem 1999;274:4722–4734.
   PubMed Web of Science ®Google Scholar
• Rigobello MP, Callegaro MP, Barzon E, Benetti M, Bindoli A. Purification of mitochondrial thioredoxin reductase and its involvement in the redox regulation of membrane permeability. Free Radic Biol Med 1998;24:370–376.
   PubMed Web of Science ®Google Scholar
• Laurent TC, Moore EC, Reichard P. Enzymatic synthesis of deoxyribonucleotides. IV. Isolation and characterization of thioredoxin, the hydrogen donor from Escherichia Coli B. J Biol Chem 1964;239:3436–3444.
   PubMed Web of Science ®Google Scholar
• Levine RL, Moskovitz J, Stadtman ER. Oxidation of methionine in proteins: roles in antioxidant defense and cellular regulation. IUBMB Life 2000;50:301–307.
   PubMed Web of Science ®Google Scholar
• Hofmann B, Hecht HJ, Flohé L. Peroxiredoxins. Biol Chem 2002;383:347–364.
   PubMed Web of Science ®Google Scholar
• Rhee SG, Chae HY, Kim K. Peroxiredoxins: a historical overview and speculative preview of novel mechanisms and emerging concepts in cell signaling. Free Radic Biol Med 2005;38:1543–1552.
   PubMed Web of Science ®Google Scholar
• Saitoh M, Nishitoh H, Fujii M, Takeda K, Tobiume K, Sawada Y, Kawabata M, Miyazono K, Ichijo H. Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1. EMBO J 1998;17:2596–2606.
   PubMed Web of Science ®Google Scholar
• Liu H, Zhang H, Iles KE, Rinna A, Merrill G, Yodoi J, Torres M, Forman HJ. The ADP-stimulated NADPH oxidase activates the ASK-1/MKK4/JNK pathway in alveolar macrophages. Free Radic Res 2006;40:865–874.
   PubMed Web of Science ®Google Scholar
• Morel Y, Barouki R. Repression of gene expression by oxidative stress. Biochem J 1999;342:481–496.
   PubMed Web of Science ®Google Scholar
• Welsh SJ, Bellamy WT, Briehl MM, Powis G. The redox protein thioredoxin-1 (Trx-1) increases hypoxia-inducible factor 1alpha protein expression: Trx-1 overexpression results in increased vascular endothelial growth factor production and enhanced tumor angiogenesis. Cancer Res 2002;62:5089–5095.
   PubMed Web of Science ®Google Scholar
• Makino Y, Yoshikawa N, Okamoto K, Hirota K, Yodoi J, Makino I, Tanaka H. Direct association with thioredoxin allows redox regulation of glucocorticoid receptor function. J Biol Chem 1999;274:3182–3188.
   PubMed Web of Science ®Google Scholar
• Ueno M, Masutani H, Arai RJ, Yamauchi A, Hirota K, Sakai T, Inamoto T, Yamaoka Y, Yodoj J, Nikaido T. Thioredoxin-dependent redox regulation of p53-mediated p21 activation. J Biol Chem 1999;274:35809–35815.
   PubMed Web of Science ®Google Scholar
• Yodoi J, Nakamura H, Masutani H. Redox regulation of stress signals: possible roles of dendritic stellate TRX producer cells (DST cell types). Biol Chem 2002;383:585–590.
   PubMed Web of Science ®Google Scholar
• Okuyama H, Nakamura H, Shimahara Y, Uyama N, Kwon Y-W, Kawada N, Yamaoka Y, Yodoi J. Overexpression of thioredoxin prevents thioacetamide-induced hepatic fibrosis in mice. J Hepatol 2005;42:117–123.
   PubMedGoogle Scholar
• Matsumoto K, Masutani H, Nishiyama A, Hashimoto S, Gon Y, Horie T, Yodoi J. C-propeptide region of human proα1 type 1 collagen interacts with thioredoxin. Biochem Biophys Res Commun 2002;295:663–667.
   PubMedGoogle Scholar
• Ohashi S, Nishio A, Nakamura A, Asada M, Tamaki H, Kawasaki K, Fukui T, Yodoi J, Chiba T. Overexpression of redox-active protein thioredoxin-1 prevents development of chronic pancreatitis in mice. Antioxid Redox Signal 2006;8:1835–1845.
   PubMedGoogle Scholar
• Okuyama H, Son A, Ahsan MK, Masutani H, Nakamura H, Yodoi J. Thioredoxin and thioredoxin binding protein 2 in the liver. IUBMB Life 2008;60:656–660.
   PubMedGoogle Scholar
• Urig S, Becker K. On the potential of thioredoxin reductase inhibitors for cancer therapy. Sem Cancer Biol 2006;16:452–465.
   PubMed Web of Science ®Google Scholar
• Bindoli A, Rigobello MP, Scutari G, Gabbiani C, Casini A, Messori L. Thioredoxin reductase: a target for gold compounds acting as potential anticancer drugs. Coord Chem Rev 2009;253:1692–1707.
   Web of Science ®Google Scholar
• Fang J, Holmgren A. Inhibition of thioredoxin and thioredoxin reductase by 4-hydroxy-2-nonenal in vitro and in vivo. J Am Chem Soc 2006;128:1879–1885.
   PubMed Web of Science ®Google Scholar
• Casini A, Pellegrini G, Ceni E, Salzano R, Parola M, Robino G, Milani S, Dianzani MU, Surrenti C. Human hepatic stellate cells express class I alcohol dehydrogenase and aldehyde dehydrogenase but not cytochrome P4502E1. J Hepatol 1998;28:40–45.
   PubMedGoogle Scholar
• Yamauchi M, Potter JJ, Mezey E. Characteristics of alchol dehydrogenase in fat-storing (Ito) cells of rat liver. Gastroenterology 1988;94:163–169.
   PubMedGoogle Scholar
• Choi HS, Shim JS, Kim J-A, Kang SW, Kwon HJ. Discovery of gliotoxin as a new small molecule targeting thioredoxin redox system. Biochem Biophys Res Commun 2007;359:523–528.
   PubMedGoogle Scholar
• Cox AG, Brown KK, Arnér ESJ, Hampton MB. The thioredoxin reductase inhibitor auranofin triggers apoptosis through a Bax/Bak-dependent process that involves peroxiredoxin 3 oxidation. Biochem Pharmacol 2008;76:1097–1109.
   PubMed Web of Science ®Google Scholar
• Kim P-K, Kim M-R, Kim H-J, Yoo H-S, Kim J-S, Cho E-H, Kim C-W. Proteome analysis of the rat hepatic stellate cells under high concentrations of glucose. Proteomics 2007;7:2184–2188.
   PubMedGoogle Scholar
• Iredale JP, Benyon RC, Pickering J, McCullen M, Northrop M, Pawley S, Howell C, Arthur MJ. Mechanisms of spontaneous resolution of rat liver fibrosis. Hepatic stellate cell apoptosis and reduced hepatic expression of metalloproteinase inhibitors. J Clin Invest 1998;102:538–549.
   PubMed Web of Science ®Google Scholar
• Oakley F, Meso M, Iredale JP, Green K, Marek CJ, Zhou X, May MJ, Millward-Sadler H, Wright MC, Mann DA. Inhibition of inhibitor of kappa-B kinases stimulates hepatic stellate cell apoptosis and accelerated recovery from rat liver fibrosis. Gastroenterology 2005;128:108–120.
   PubMed Web of Science ®Google Scholar
• Wright MC, Issa R, Smart DE, Trim N, Murray GI, Primrose JN, Arthur MJP, Iredale JP, Mann DA. Gliotoxin stimulates the apoptosis of human and rat hepatic stellate cells and enhances the resolution of liver fibrosis in rats. Gastroenterology 2001;121:685–698.
   PubMed Web of Science ®Google Scholar
• Bataller R, Brenner DA. Hepatic stellate cells as a target for the treatment of liver fibrosis. Sem Liver Dis 2001;21:437–451.
   PubMed Web of Science ®Google Scholar
• Kisseleva T, Brenner D. Hepatic stellate cells and the reversal of fibrosis. J Gastroenterol Hepatol 2006;21:S84–S87.
   PubMed Web of Science ®Google Scholar
• Thirunavukkarasu C, Watkins S, Harvey SAK, Gandhi CR. Superoxide-induced apoptosis of activated rat hepatic stellate cells. J Hepatol 2004;41:567–575.
   PubMed Web of Science ®Google Scholar
• Novo E, Marra F, Zamara E, Valfrè di Bonzo L, Caligiuri A, Cannito S, Antonaci C, Colombatto S, Pinzani M, Parola M. Dose dependent and divergent effects of superoxide anion on cell death, proliferation, and migration of activated human hepatic stellate cells. Gut 2006;55:90–97.
   PubMedGoogle Scholar
• Dunning S, Hannivoort RA, De Boer JF, Buist-Homan M, Faber KN, Moshage H. Superoxide anions and hydrogen peroxide inhibit proliferation of activated rat stellate cells and induce different modes of cell death. Liver Int 2009;29:922–932.
   PubMedGoogle Scholar
• Langer DA, Das A, Semela D, Kang-Decker N, Hendrickson H, Bronk SF, Katusic ZS, Gores GJ, Vijay H. Shah VH. Nitric oxide promotes caspase-independent hepatic stellate cell apoptosis through the generation of reactive oxygen species. Hepatology 2008;47:1983–1993.
   PubMed Web of Science ®Google Scholar
• Siegmund SV, Uchinami H, Osawa Y, Brenner DA, Schwabe RF. Anandamide induces necrosis in primary hepatic stellate cells. Hepatology 2005;41:1085–1095.
   PubMed Web of Science ®Google Scholar
• Julien B, Grenard P, Teixeira-Clerc F, Van Nhieu JT, Li L, Karsak M, Zimmer A, Mallat A, Lotersztajn S. Antifibrogenic role of the cannabinoid receptor CB2 in the liver. Gastroenterology 2005;128:742–755.
   PubMed Web of Science ®Google Scholar
• Teixeira-Clerc F, Julien B, Grenard P, Tran Van Nhieu J, Deveaux V, Li L, Serriere-Lanneau V, Ledent C, Mallat A, Lotersztajn S. CB1 cannabinoid receptor antagonism: a new strategy for the treatment of liver fibrosis. Nat Med 2006;12:271–276.
   Google Scholar
• Siegmund SV, Seki E, Osawa Y, Uchinami H, Cravatt BF, Schwabe RF. Fatty acid amide hydrolase determines anandamide-induced cell death in the liver. J Biol Chem 2006;281:10431–10438.
   PubMed Web of Science ®Google Scholar
• Costantini P, Belzacq AS, Vieira HL, Rochette N, de Pablo MA, Zamzami N, Susin SA, Brenner C, Kroemer G. Oxidation of a critical thiol residue of the adenine nucleotide translocator enforces Bcl-2 independent permeability transition pore opening and apoptosis. Oncogene 2000;19:307–314.
   PubMed Web of Science ®Google Scholar
• Madesh M, Hajnoczky G. VDAC-dependent permeabilization of the outer mitochondrial membrane by superoxide induces rapid and massive cytochrome c release. J Cell Biol 2001;155:1003–1015.
   PubMed Web of Science ®Google Scholar
• Bataller R, Schwabe RF, Choi YH, Yang L, Paik YH, Lindquist J, Qian T, Schoonhoven R, Hagedorn CH, Lemasters JJ, Brenner DA. NADPH oxidase signal transduces angiotensin II in hepatic stellate cells and is critical in hepatic fibrosis. J Clin Invest 2003;112:1383–1394.
   PubMed Web of Science ®Google Scholar
• Galli A, Svegliati-Baroni G, Ceni E, Milani S, Ridolfi F, Salzano R, Tarocchi M, Grappone C, Pellegrini G, Benedetti A, Surrenti C, Casini A. Oxidative stress stimulates proliferation and invasiveness of hepatic stellate cells via a MMP2-mediated mechanism. Hepatology 2005;41:1074–1084.
   PubMed Web of Science ®Google Scholar
• Lang A, Schoonhoven R, Tuvia S, Brenner DA, Rippe RA. Nuclear factor k-B in proliferation, activation and apoptosis in rat hepatic stellate cells. J Hepatol 2000;33:49–58.
   PubMed Web of Science ®Google Scholar
• Saile B, Knittel T, Matthes N, Schott P, Ramadori G. CD95/CD95L-mediated apoptosis of the hepatic stellate cell. A mechanism terminating uncontrolled hepatic stellate cell proliferation during hepatic tissue repair. Am J Pathol 1997;151:1265–1272.
   PubMed Web of Science ®Google Scholar
• Hagens WI, Beljaars L, Mann DA, Wright MC, Julien B, Lotersztajn S, Reker-Smit C, Poelstra K. Cellular targeting of the apoptosis-inducing compound gliotoxin to fibrotic rat livers. J Pharmacol Exp Ther 2008;324:902–910.
   PubMed Web of Science ®Google Scholar
• Kweon Y-O, Paik Y-H, Schnabl B, Qian T, Lemasters JJ, Brenner DA. Gliotoxin-mediated apoptosis of activated human hepatic stellate cells. J Hepatol 2003;39:38–46.
   PubMed Web of Science ®Google Scholar
• Souza IC, Martins LAM, Coelho BP, Grivicich I, Guaragna RM, Gottfried C, Borojevic R, Guma FCR. Resveratrol inhibits cell growth by inducing cell cycle arrest in activated hepatic stellate cells. Mol Cell Biochem 2008;315:1–7.
   PubMedGoogle Scholar
• Bechmann LP, Zahn D, Gieseler RK, Fingas CD, Marquitan G, Jochum C, Gerken G, Friedman SL, Canbay A. Resveratrol amplifies profibrogenic effects of free fatty acids on human hepatic stellate cells. Hepatol Res 2009;39:601–608.
   PubMedGoogle Scholar
• Refik Mas M, Comert B, Oncu K, Vural SA, Akay C, Tasci I, Ozkomur E, Serdar M, Mas N, Alcigir G, Yener N. The effect of taurine treatment on oxidative stress in experimental liver fibrosis. Hepatology Res 2004;28:207–215.
   PubMedGoogle Scholar
• Kim JY, Kim KM, Nan J-X, Zhao YZ, Park P-H, Lee SJ, Sohn DH. Induction of apoptosis by tanshinone I via cytochrome c release in activated hepatic stellate cells. Pharmacol Toxicol 2003;92:195–200.
   PubMedGoogle Scholar
• Tang X, Yang J, Li J. Accelerative effect of leflunomide on recovery from hepatic fibrosis involves TRAIL-mediated hepatic stellate cell apoptosis. Life Sci 2009;84:552–557.
   PubMedGoogle Scholar
• Paik YH, Kim JK, Lee JI, Kang SH, Kim DY, An SH, Lee SJ, Lee DK, Han KH, Chon CY, Lee SI, Lee KS, Brenner DA. Celecoxib induces hepatic stellate cell apoptosis through inhibition of Akt activation and suppresses hepatic fibrosis in rats. Gut 2009;58:1517–1527.
   PubMed Web of Science ®Google Scholar
• Lin Y-L, Lin C-Y, Chi C-W, Huang Y-T. Study on antifibrotic effects of curcumin in rat hepatic stellate cells. Phytother Res 2009;23:927–932.
   PubMedGoogle Scholar
• Myung SJ, Yoon J-H, Kim B-H, Lee J-H, Jung EU, Lee H-S. Heat shock protein 90 inhibitor induces apoptosis and attenuates activation of hepatic stellate cells. J Pharmacol Exp Ther 2009;330:276–282.
   PubMedGoogle Scholar
• Radaeva S, Sun R, Jaruga B, Nguyen VT, Tian Z, Gao B. Natural killer cells ameliorate liver fibrosis by killing activated stellate cells in NKG2D-dependent and tumor necrosis factor-related apoptosis-inducing ligand-dependent manners. Gastroenterology 2006;130:435–452.
   PubMed Web of Science ®Google Scholar
• Ogawa T, Kawada N, Ikeda K. Effect of natural interferon α on proliferation and apoptosis of hepatic stellate cells. Hepatol Int 2009;3:497–503.
   PubMed Web of Science ®Google Scholar
• Lambeth JD. NOX enzymes and the biology of reactive oxygen. Nat Rev Immunol 2004;4:181–189.
   PubMed Web of Science ®Google Scholar
• Quinn MT, Gauss KA. Structure and regulation of the neutrophil respiratory burst oxidase: comparison with nonphagocyte oxidases. J Leukoc Biol 2004;76:760–781.
   PubMed Web of Science ®Google Scholar
• Sumimoto H. Structure, regulation and evolution of Nox-family NADPH oxidases that produce reactive oxygen species. FEBS J 2008;275:3249–3277.
   PubMed Web of Science ®Google Scholar
• Vignais PV. The superoxide-generating NADPH oxidase: structural aspects and activation mechanism. Cell Mol Life Sci 2002;59:1428–1459.
   PubMed Web of Science ®Google Scholar
• El-Benna J, Dang PM, Gougerot-Pocidalo MA, Elbim C. Phagocyte NADPH oxidase: a multicomponent enzyme essential for host defenses. Arch Immunol Ther Exp (Warsz) 2005;53:199–206.
   PubMed Web of Science ®Google Scholar
• Bokoch GM, Diebold BA. Current molecular models for NADPH oxidase regulation by Rac GTPase. Blood 2002;100:2692–2696.
   PubMed Web of Science ®Google Scholar
• Ago T, Kuribayashi F, Hiroaki H, Takeya R, Ito T, Kohda D, Sumimoto H. Phosphorylation of p47phox directs phox homology domain from SH3 domain toward phosphoinositides, leading to phagocyte NADPH oxidase activation. Proc Natl Acad Sci USA 2003;100:4474–4479.
   PubMed Web of Science ®Google Scholar
• De Minicis S, Bataller R, Brenner DA. NADPH oxidase in the liver: defensive, offensive, or fibrogenic? Gastroenterology 2006;131:272–275.
   PubMed Web of Science ®Google Scholar
• Adachi T, Togashi H, Suzuki A, Kasai S, Ito J, Sugahara K, Kawata S. NAD(P)H oxidase plays a crucial role in PDGF-induced proliferation of hepatic stellate cells. Hepatology 2005;41:1272–1281.
   PubMed Web of Science ®Google Scholar
• Jiang JX, Mikami K, Shah VH, Torok NJ. Leptin induces phagocytosis of apoptotic bodies by hepatic stellate cells via a Rho guanosine triphosphatase-dependent mechanism. Hepatology 2008;48:1497–1505.
   PubMedGoogle Scholar
• De Minicis S, Seki E, Oesterreicher C, Schnabl B, Schwabe RF, Brenner DA. Reduced nicotinamide adenine dinucleotide phosphate oxidase mediates fibrotic and inflammatory effects of leptin on hepatic stellate cells. Hepatology 2008;48:2016–2026.
   PubMed Web of Science ®Google Scholar
• Zhan SS, Jiang JX, Wu J, Halsted C, Friedman SL, Zern MA, Torok NJ. Phagocytosis of apoptotic bodies by hepatic stellate cells induces NADPH oxidase and is associated with liver fibrosis in vivo. Hepatology 2006;43:435–443.
   PubMed Web of Science ®Google Scholar
• Bedard K, Krause K-H. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 2007;87:245–313.
   PubMed Web of Science ®Google Scholar
• Lyle AN, Griendling KK. Modulation of vascular smooth muscle signaling by reactive oxygen species. Physiology (Bethesda) 2006;21:269–280.
   PubMed Web of Science ®Google Scholar
• Reinehr R, Sommerfeld A, Häussinger D. CD95 ligand is a proliferative and antiapoptotic signal in quiescent hepatic stellate cells. Gastroenterology 2008;134:1494–1506.
   PubMed Web of Science ®Google Scholar
• Ushio-Fukai M, Nakamura Y. Reactive oxygen species and angiogenesis: NADPH oxidase as target for cancer therapy. Cancer Lett 2008;266:37–52.
   PubMed Web of Science ®Google Scholar
• El-Benna J, Dang PMC, Gougerot-Pocidalo M-A, Marie J-C, Braut-Boucher F. p47phox, the phagocyte NADPH oxidase/NOX2 organizer: structure, phosphorylation and implication in diseases. Exp Mol Med 2009;41:217–225.
   PubMed Web of Science ®Google Scholar
• Karathanassis D, Stahelin RV, Bravo J, Perisic O, Pacold CM, Cho W, Williams RL. Binding of the PX domain of p47phox to phosphatidylinositol 3,4-bisphosphate and phosphatidic acid is masked by an intramolecular interaction. EMBO J 2002;21:5057–5068.
   PubMed Web of Science ®Google Scholar
• De Minicis S, Brenner DA. Nox in liver fibrosis. Arch Biochem Biophys 2007;462:266–272.
   PubMed Web of Science ®Google Scholar
• Chowdhury AK, Watkins T, Parinandi NL, Saatian B, Kleinberg ME, Usatyuk PV, Natarajan V. Src-mediated tyrosine phosphorylation of p47phox in hyperoxia-induced activation of NADPH oxidase and generation of reactive oxygen species in lung endothelial cells. J Biol Chem 2005;280:20700–20711.
   PubMedGoogle Scholar
• Catarzi S, Giannoni E, Favilli F, Meacci E, Iantomasi T, Vincenzini MT. Sphingosine 1-phosphate stimulation of NADPH oxidase activity: relationship with platelet-derived growth factor receptor and c-Src kinase. Biochim Biophys Acta 2007;1770:872–883.
   PubMedGoogle Scholar
• Usatyuk PV, Romer LH, He D, Parinandi NL, Kleinberg ME, Zhan S, Jacobson JR, Dudek SM, Pendyala S, Garcia JGN, Natarajan V. Regulation of hyperoxia-induced NADPH oxidase activation in human lung endothelial cells by the actin cytoskeleton and cortactin. J Biol Chem 2007;282:23284–23295.
   PubMed Web of Science ®Google Scholar
• Gianni D, Bohl B, Courtneidge SA, Bokoch GM. The involvement of the tyrosine kinase c-Src in the regulation of reactive oxygen species generation mediated by NADPH oxidase-1. Mol Biol Cell 2008;19:2984–2994.
   PubMed Web of Science ®Google Scholar
• Giannoni E, Buricchi F, Raugei G, Ramponi G, Chiarugi P. Intracellular reactive oxygen species activate Src tyrosine kinase during cell adhesion and anchorage-dependent cell growth. Mol Cell Biol 2005;25:6391–6403.
   PubMed Web of Science ®Google Scholar
• Chiarugi P. Src redox regulation: there is more than meets the eye. Mol Cells 2008;26:329–337.
   PubMed Web of Science ®Google Scholar
• Krasnowska EK, Pittaluga E, Brunati AM, Brunelli R, Costa G, De Spirito M, Serafino A, Ursini F, Parasassi T. N-acetyl-l-cysteine fosters inactivation and transfer to endolysosomes of c-Src. Free Radic Biol Med 2008;45:1566–1572.
   PubMedGoogle Scholar
• Senga T, Hasegawa H, Tanaka M, Aminur Rahman M, Ito S, Hamaguchi M. The cysteine-cluster motif of c-Src: its role for the heavy metal-mediated activation of kinase. Cancer Sci 2008;99:571–575.
   PubMedGoogle Scholar
• Brown MT, Cooper, JA. Regulation, substrates and functions of src. Biochim Biophys Acta 1996;1287:121–149.
   PubMed Web of Science ®Google Scholar
• Boggon TJ, Eck MJ. Structure and regulation of Src family kinases. Oncogene 2004;23:7918–7927.
   PubMed Web of Science ®Google Scholar
• Contri A, Brunati AM, Trentin L, Cabrelle A, Miorin M, Cesaro L, Pinna LA, Zambello R, Semenzato G, Donella-Deana A. Chronic lymphocytic leukemia B cells contain anomalous Lyn tyrosine kinase, a putative contribution to defective apoptosis. J Clin Invest 2005;115:369–378.
   PubMed Web of Science ®Google Scholar
• Hornstein I, Alcover A, Katzav S. Vav proteins, masters of the world of cytoskeleton organization. Cell Signal 2004;16:1–11.
   PubMedGoogle Scholar
• Choi SS, Sicklick JK, Ma Q, Yang L, Huang J, Qi Y, Chen W, Li Y-X, Goldschmidt-Clermont PJ, Diehl AM. Sustained activation of Rac1 in hepatic stellate cells promotes liver injury and fibrosis in mice. Hepatology 2006;44:1267–1277.
   PubMed Web of Science ®Google Scholar