Activation of autophagy protects against cholestasis-induced hepatic injury

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• 作者：Lu Gao (1)
  Gang Lv (2)
  Xianling Guo (1)
  Yingying Jing (1)
  Zhipeng Han (1)
  Shanshan Zhang (1)
  Kai Sun (3)
  Rong Li (1)
  Yang Yang (1)
  Lixin Wei (1) (3)
  
  1. Tumor Immunology and Gene Therapy Center ; Eastern Hepatobiliary Surgery Hospital ; The Second Military Medical University ; 225 Changhai Road ; Shanghai ; 200438 ; China
  2. Department of Hepatic Surgery ; Eastern Hepatobiliary Surgery Hospital ; The Second Military Medical University ; Shanghai ; China
  3. Central laboratory ; Renji hospital ; Shanghai Jiaotong University School of Medicine ; Shanghai ; China
  
• 关键词：Autophagy ; Bile acid ; Cholestasis ; Hepatocyte ; Reactive oxygen species
• 刊名：Cell & Bioscience
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：4
• 期：1
• 全文大小：2,560 KB
• 参考文献：1. Guicciardi, ME, Gores, GJ (2002) Bile acid-mediated hepatocyte apoptosis and cholestatic liver disease. Dig Liver Dis 34: pp. 387-392 CrossRef
  2. Reichel, C, Meier-Abt, PJ (1997) Cholestatic liver diseases. Ther Umsch 54: pp. 639-644
  3. Karvonen, J, Kairisto, V, Gronroos, JM (2006) Stone or stricture as a cause of extrahepatic cholestasis鈥揹o liver function tests predict the diagnosis?. Clin Chem Lab Med 44: pp. 1453-1456 CrossRef
  4. Zhangxue, H, Min, G, Jinning, Z, Yuan, S, Li, W, Huapei, S, Rui, L, Chunyu, Z (2012) Glycochenodeoxycholate induces rat alveolar epithelial type II cell death and inhibits surfactant secretion in vitro. Free Radic Biol Med 53: pp. 122-128 CrossRef
  5. Heuman, DM, Mills, AS, McCall, J, Hylemon, PB, Pandak, WM, Vlahcevic, ZR (1991) Conjugates of ursodeoxycholate protect against cholestasis and hepatocellular necrosis caused by more hydrophobic bile salts. In vivo studies in the rat. Gastroenterology 100: pp. 203-211
  6. Schmucker, DL, Ohta, M, Kanai, S, Sato, Y, Kitani, K (1990) Hepatic injury induced by bile salts: correlation between biochemical and morphological events. Hepatology 12: pp. 1216-1221 CrossRef
  7. Schoemaker, MH, Gommans, WM, de la Conde Rosa, L, Homan, M, Klok, P, Trautwein, C, van Goor, H, Poelstra, K, Haisma, HJ, Jansen, PL, Moshage, H (2003) Resistance of rat hepatocytes against bile acid-induced apoptosis in cholestatic liver injury is due to nuclear factor-kappa B activation. J Hepatol 39: pp. 153-161 CrossRef
  8. Patel, T, Bronk, SF, Gores, GJ (1994) Increases of intracellular magnesium promote glycodeoxycholate-induced apoptosis in rat hepatocytes. J Clin Invest 94: pp. 2183-2192 CrossRef
  9. Czaja, MJ (2011) Functions of autophagy in hepatic and pancreatic physiology and disease. Gastroenterology 140: pp. 1895-1908 CrossRef
  10. Yorimitsu, T, Klionsky, DJ (2005) Autophagy: molecular machinery for self-eating. Cell Death Differ 12: pp. 1542-1552 CrossRef
  11. Moreau, K, Luo, S, Rubinsztein, DC (2010) Cytoprotective roles for autophagy. Curr Opin Cell Biol 22: pp. 206-211 CrossRef
  12. Kuma, A, Matsui, M, Mizushima, N (2007) LC3, an autophagosome marker, can be incorporated into protein aggregates independent of autophagy: caution in the interpretation of LC3 localization. Autophagy 3: pp. 323-328 CrossRef
  13. Mathew, R, Karp, CM, Beaudoin, B, Vuong, N, Chen, G, Chen, HY, Bray, K, Reddy, A, Bhanot, G, Gelinas, C, Dipaola, RS, Karantza-Wadsworth, V, White, E (2009) Autophagy suppresses tumorigenesis through elimination of p62. Cell 137: pp. 1062-1075 CrossRef
  14. Narendra, D, Kane, LA, Hauser, DN, Fearnley, IM, Youle, RJ (2010) p62/SQSTM1 is required for Parkin-induced mitochondrial clustering but not mitophagy; VDAC1 is dispensable for both. Autophagy 6: pp. 1090-1106 CrossRef
  15. Manley, S, Williams, JA, Ding, WX (2013) Role of p62/SQSTM1 in liver physiology and pathogenesis. Exp Biol Med (Maywood) 238: pp. 525-538 CrossRef
  16. Arroyo, DS, Gaviglio, EA, Peralta Ramos, JM, Bussi, C, Rodriguez-Galan, MC, Iribarren, P (2014) Autophagy in inflammation, infection, neurodegeneration and cancer. Int Immunopharmacol 18: pp. 55-65 CrossRef
  17. Ding, WX, Li, M, Chen, X, Ni, HM, Lin, CW, Gao, W, Lu, B, Stolz, DB, Clemens, DL, Yin, XM (2010) Autophagy reduces acute ethanol-induced hepatotoxicity and steatosis in mice. Gastroenterology 139: pp. 1740-1752 CrossRef
  18. Igusa, Y, Yamashina, S, Izumi, K, Inami, Y, Fukada, H, Komatsu, M, Tanaka, K, Ikejima, K, Watanabe, S (2012) Loss of autophagy promotes murine acetaminophen hepatotoxicity. J Gastroenterol 47: pp. 433-443 CrossRef
  19. Ni, HM, Bockus, A, Boggess, N, Jaeschke, H, Ding, WX (2012) Activation of autophagy protects against acetaminophen-induced hepatotoxicity. Hepatology 55: pp. 222-232 CrossRef
  20. Singh, R, Kaushik, S, Wang, Y, Xiang, Y, Novak, I, Komatsu, M, Tanaka, K, Cuervo, AM, Czaja, MJ (2009) Autophagy regulates lipid metabolism. Nature 458: pp. 1131-1135 CrossRef
  21. Kabeya, Y, Mizushima, N, Ueno, T, Yamamoto, A, Kirisako, T, Noda, T, Kominami, E, Ohsumi, Y, Yoshimori, T (2000) LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 19: pp. 5720-5728 CrossRef
  22. Yerushalmi, B, Dahl, R, Devereaux, MW, Gumpricht, E, Sokol, RJ (2001) Bile acid-induced rat hepatocyte apoptosis is inhibited by antioxidants and blockers of the mitochondrial permeability transition. Hepatology 33: pp. 616-626 CrossRef
  23. Sokol, RJ, Winklhofer-Roob, BM, Devereaux, MW, McKim, JM (1995) Generation of hydroperoxides in isolated rat hepatocytes and hepatic mitochondria exposed to hydrophobic bile acids. Gastroenterology 109: pp. 1249-1256 CrossRef
  24. Maes, M, Mihaylova, I, Kubera, M, Uytterhoeven, M, Vrydags, N, Bosmans, E (2009) Increased 8-hydroxy-deoxyguanosine, a marker of oxidative damage to DNA, in major depression and myalgic encephalomyelitis/chronic fatigue syndrome. Neuro Endocrinol Lett 30: pp. 715-722
  25. Lin, CW, Zhang, H, Li, M, Xiong, X, Chen, X, Dong, XC, Yin, XM (2013) Pharmacological promotion of autophagy alleviates steatosis and injury in alcoholic and non-alcoholic fatty liver conditions in mice. J Hepatol 58: pp. 993-999 CrossRef
  26. Osna, NA, Thomes, PG, Jr, TM (2011) Involvement of autophagy in alcoholic liver injury and hepatitis C pathogenesis. World J Gastroenterol 17: pp. 2507-2514 CrossRef
  27. Sun, K, Xie, X, Liu, Y, Han, Z, Zhao, X, Cai, N, Zhang, S, Song, J, Wei, L (2013) Autophagy lessens ischemic liver injury by reducing oxidative damage. Cell Biosci 3: pp. 26 CrossRef
  28. Yun, N, Cho, HI, Lee, SM (2014) Impaired autophagy contributes to hepatocellular damage during ischemia/reperfusion: heme oxygenase-1 as a possible regulator. Free Radic Biol Med 68: pp. 168-177 CrossRef
  29. Rautou, PE, Mansouri, A, Lebrec, D, Durand, F, Valla, D, Moreau, R (2010) Autophagy in liver diseases. J Hepatol 53: pp. 1123-1134 CrossRef
  30. Shiomi, M, Miyamae, M, Takemura, G, Kaneda, K, Inamura, Y, Onishi, A, Koshinuma, S, Momota, Y, Minami, T, Figueredo, VM (2014) Induction of autophagy restores the loss of sevoflurane cardiac preconditioning seen with prolonged ischemic insult. Eur J Pharmacol 724: pp. 58-66 CrossRef
  31. Loos, B, Genade, S, Ellis, B, Lochner, A, Engelbrecht, AM (2011) At the core of survival: autophagy delays the onset of both apoptotic and necrotic cell death in a model of ischemic cell injury. Exp Cell Res 317: pp. 1437-1453 CrossRef
  32. Ding, ZB, Hui, B, Shi, YH, Zhou, J, Peng, YF, Gu, CY, Yang, H, Shi, GM, Ke, AW, Wang, XY, Song, K, Dai, Z, Shen, YH, Fan, J (2011) Autophagy activation in hepatocellular carcinoma contributes to the tolerance of oxaliplatin via reactive oxygen species modulation. Clin Cancer Res 17: pp. 6229-6238 CrossRef
  33. Kanki, T (2010) Nix, a receptor protein for mitophagy in mammals. Autophagy 6: pp. 433-435 CrossRef
  34. Tsai, LY, Lee, KT, Liu, TZ (1998) Evidence for accelerated generation of hydroxyl radicals in experimental obstructive jaundice of rats. Free Radic Biol Med 24: pp. 732-737 CrossRef
  
• 刊物主题：Cell Biology; Microbiology;
• 出版者：BioMed Central
• ISSN：2045-3701

文摘

Background Cholestasis is characterized by an abnormal accumulation of bile acids and causes hepatocellular injury. Recent studies show that autophagy is involved in the pathophysiology of many liver diseases. The potential role of autophagy in preventing cholestatic hepatotoxicity, however, has rarely been investigated. The aim of this study was to examine whether autophagy is involved in the cholestatic hepatotoxicity. Results We found that bile duct ligation (BDL) led to cholestatic liver injury and hepatocytic autophagy activation in the mice. Suppression of autophagy with Chloroquine (CQ) increased liver injury and hepatocytes apoptosis; while activation of autophagy by rapamycin reduced cholestasis hepatotoxicity. In L02 normal liver cells, Glycochenodeoxycholate (GCDC) treatment would induce autophagy. Inhibition of autophagy by CQ could promote GCDC-induced cell apoptosis. In contrast, rapamycin treatment could protect against GCDC-induced cell death. Furthermore, autophagy contributed to the liver cells survival via modulation of reactive oxygen species (ROS). Conclusions These findings indicate that autophagy protects against cholestasis induced liver injury and hepatocyte apoptosis by eliminating ROS accumulation. Our data suggest that enhancement of autophagy may be a therapeutic strategy to mitigate cholestatic liver injury.