Autophagy protects against palmitate-induced apoptosis in hepatocytes

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• 作者：Ning Cai ; Xue Zhao ; Yingying Jing ; Kai Sun ; Shufan Jiao ; Xiaojing Chen…
• 关键词：Autophagy ; Palmitate ; Hepatocytes ; Apoptosis ; Protector
• 刊名：Cell & Bioscience
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：4
• 期：1
• 全文大小：1,216 KB
• 参考文献：1. Papandreou, D, Rousso, I, Mavromichalis, I (2007) Update on non-alcoholic fatty liver disease in children. Clin Nutr 26: pp. 409-415 CrossRef
  2. Marchesini, G, Moscatiello, S, Agostini, F, Villanova, N, Festi, D (2011) Treatment of non-alcoholic fatty liver disease with focus on emerging drugs. Expert Opin Emerg Drugs 16: pp. 121-136 CrossRef
  3. Gerber, L, Otgonsuren, M, Mishra, A, Escheik, C, Birerdinc, A, Stepanova, M, Younossi, ZM (2012) Non-alcoholic fatty liver disease (NAFLD) is associated with low level of physical activity: a population-based study. Aliment Pharmacol Ther 36: pp. 772-781 CrossRef
  4. Bugianesi, E, Leone, N, Vanni, E, Marchesini, G, Brunello, F, Carucci, P, Musso, A, De Paolis, P, Capussotti, L, Salizzoni, M, Rizzetto, M (2002) Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterol 123: pp. 134-140 CrossRef
  5. Barshop, NJ, Sirlin, CB, Schwimmer, JB, Lavine, JE (2008) Review article: epidemiology, pathogenesis and potential treatments of paediatric non-alcoholic fatty liver disease. Aliment Pharmacol Ther 28: pp. 13-24 CrossRef
  6. Rossi, F, Bellini, G, Alisi, A, Alterio, A, Maione, S, Perrone, L, Locatelli, F, Miraglia Del Giudice, E, Nobili, V (2012) Cannabinoid receptor type 2 functional variant influences liver damage in children with non-alcoholic fatty liver disease. PLoS One 7: pp. e42259 CrossRef
  7. Adams, LA, Angulo, P (2006) Treatment of non-alcoholic fatty liver disease. Postgrad Med J 82: pp. 315-322 CrossRef
  8. Niklas, J, Bonin, A, Mangin, S, Bucher, J, Kopacz, S, Matz-Soja, M, Thiel, C, Gebhardt, R, Hofmann, U, Mauch, K (2012) Central energy metabolism remains robust in acute steatotic hepatocytes challenged by a high free fatty acid load. BMB Rep 45: pp. 396-401 CrossRef
  9. McCullough, AJ (2006) Pathophysiology of nonalcoholic steatohepatitis. J Clin Gastroenterol 40: pp. S17-S29
  10. Barreyro, FJ, Kobayashi, S, Bronk, SF, Werneburg, NW, Malhi, H, Gores, GJ (2007) Transcriptional regulation of Bim by FoxO3A mediates hepatocyte lipoapoptosis. J Biol Chem 282: pp. 27141-27154 CrossRef
  11. Cazanave, SC, Mott, JL, Elmi, NA, Bronk, SF, Werneburg, NW, Akazawa, Y, Kahraman, A, Garrison, SP, Zambetti, GP, Charlton, MR, Gores, GJ (2009) JNK1-dependent PUMA expression contributes to hepatocyte lipoapoptosis. J Biol Chem 284: pp. 26591-26602 CrossRef
  12. Al-Fehaily, M, Clark, OH (2003) Persistent or recurrent primary hyperparathyroidism. Annali italiani di chirurgia 74: pp. 423-434
  13. Han, CW, Kang, ES, Ham, SA, Woo, HJ, Lee, JH, Seo, HG (2012) Antioxidative effects of Alisma orientale extract in palmitate-induced cellular injury. Pharm Biol 50: pp. 1281-1288 CrossRef
  14. Gentile, CL, Pagliassotti, MJ (2008) The role of fatty acids in the development and progression of nonalcoholic fatty liver disease. J Nutr Biochem 19: pp. 567-576 CrossRef
  15. Luo, X, Yang, Y, Shen, T, Tang, X, Xiao, Y, Zou, T, Xia, M, Ling, W (2012) Docosahexaenoic acid ameliorates palmitate-induced lipid accumulation and inflammation through repressing NLRC4 inflammasome activation in HepG2 cells. Nutr Metab 9: pp. 34 CrossRef
  16. Klionsky, DJ, Abdalla, FC, Abeliovich, H, Abraham, RT, Acevedo-Arozena, A, Adeli, K, Agholme, L, Agnello, M, Agostinis, P, Aguirre-Ghiso, JA, Ahn, HJ, Ait-Mohamed, O, Ait-
• 刊物主题：Cell Biology; Microbiology;
• 出版者：BioMed Central
• ISSN：2045-3701

文摘

Background Non-alcoholic fatty liver disease, one of the most common liver diseases, has obtained increasing attention. Palmitate (PA)-induced liver injury is considered a risk factor for the development of non-alcoholic fatty liver disease. Autophagy, a cellular degradative pathway, is an important self-defense mechanism in response to various stresses. In this study, we investigated whether autophagy plays a protective role in the progression of PA-induced hepatocytes injury. Results Annexin V-FITC/PI staining by FCM analysis, TUNEL assay and the detection of PARP and cleaved caspase3 expression levels demonstrated that PA treatment prominently induced the apoptosis of hepatocytes. Meanwhile, treatment of PA strongly induced the formation of GFP-LC3 dots, the conversion from LC3I to LC3II, the decrease of p62 protein levels and the increase of autophagosomes. These results indicated that PA also induced autophagy activation. Autophagy inhibition through chloroquine pretreatment or Atg5shRNA infection led to the increase of cell apoptosis after PA treatment. Moreover, induction of autophagy by pretreatment with rapamycin resulted in distinct decrease of PA-induced apoptosis. Therefore, autophagy can prevent hepatocytes from PA-induced apoptosis. In the further study, we explored pathway of autophagy activation in PA-treated hepatocytes. We found that PA activated PKCα in hepatocytes, and had no influence on mammalian target of rapamycin and endoplasmic reticulum stress pathways. Conclusions These results demonstrated that autophagy plays a protective role in PA-induced hepatocytes apoptosis. And PA might induce autophagy through activating PKCα pathway in hepatocytes.