Display options
Cite
Gao L, Lv G, Guo X, et al. Activation of autophagy protects against cholestasis-induced hepatic injury. Cell Biosci. 2014;4:47doi: 10.1186/2045-3701-4-47.
Gao, L., Lv, G., Guo, X., Jing, Y., Han, Z., Zhang, S., Sun, K., Li, R., Yang, Y., & Wei, L. (2014). Activation of autophagy protects against cholestasis-induced hepatic injury. Cell & bioscience, 447. https://doi.org/10.1186/2045-3701-4-47
Gao, Lu, et al. "Activation of autophagy protects against cholestasis-induced hepatic injury." Cell & bioscience vol. 4 (2014): 47. doi: https://doi.org/10.1186/2045-3701-4-47
Gao L, Lv G, Guo X, Jing Y, Han Z, Zhang S, Sun K, Li R, Yang Y, Wei L. Activation of autophagy protects against cholestasis-induced hepatic injury. Cell Biosci. 2014 Aug 26;4:47. doi: 10.1186/2045-3701-4-47. eCollection 2014. PMID: 25922659; PMCID: PMC4412295.
Copy Download .nbib Format: NLM
Share it on

Cell Biosci. 2014 Aug 26;4:47. doi: 10.1186/2045-3701-4-47. eCollection 2014.

Activation of autophagy protects against cholestasis-induced hepatic injury.

Cell & bioscience

Lu Gao, Gang Lv, Xianling Guo, Yingying Jing, Zhipeng Han, Shanshan Zhang, Kai Sun, Rong Li, Yang Yang, Lixin Wei

Affiliations

  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.
  4. Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, 225 Changhai Road, Shanghai, 200438 China ; Central laboratory, Renji hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

PMID: 25922659 PMCID: PMC4412295 DOI: 10.1186/2045-3701-4-47

Abstract

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.

Keywords: Autophagy; Bile acid; Cholestasis; Hepatocyte; Reactive oxygen species

References

  1. J Gastroenterol. 2012 Apr;47(4):433-43 - PubMed
  2. Ther Umsch. 1997 Nov;54(11):639-44 - PubMed
  3. J Hepatol. 2013 May;58(5):993-9 - PubMed
  4. Exp Biol Med (Maywood). 2013 May;238(5):525-38 - PubMed
  5. Gastroenterology. 2010 Nov;139(5):1740-52 - PubMed
  6. Autophagy. 2010 Apr;6(3):433-5 - PubMed
  7. World J Gastroenterol. 2011 May 28;17 (20):2507-14 - PubMed
  8. Gastroenterology. 2011 Jun;140(7):1895-908 - PubMed
  9. Nature. 2009 Apr 30;458(7242):1131-5 - PubMed
  10. Autophagy. 2010 Nov;6(8):1090-106 - PubMed
  11. Free Radic Biol Med. 1998 Mar 15;24(5):732-7 - PubMed
  12. EMBO J. 2000 Nov 1;19(21):5720-8 - PubMed
  13. Eur J Pharmacol. 2014 Feb 5;724:58-66 - PubMed
  14. J Hepatol. 2003 Aug;39(2):153-61 - PubMed
  15. Clin Cancer Res. 2011 Oct 1;17(19):6229-38 - PubMed
  16. Clin Chem Lab Med. 2006;44(12):1453-6 - PubMed
  17. J Hepatol. 2010 Dec;53(6):1123-34 - PubMed
  18. Hepatology. 2001 Mar;33(3):616-26 - PubMed
  19. Cell Death Differ. 2005 Nov;12 Suppl 2:1542-52 - PubMed
  20. Curr Opin Cell Biol. 2010 Apr;22(2):206-11 - PubMed
  21. Free Radic Biol Med. 2014 Mar;68:168-77 - PubMed
  22. Hepatology. 1990 Nov;12(5):1216-21 - PubMed
  23. Autophagy. 2007 Jul-Aug;3(4):323-8 - PubMed
  24. Exp Cell Res. 2011 Jun 10;317(10 ):1437-53 - PubMed
  25. Hepatology. 2012 Jan;55(1):222-32 - PubMed
  26. Free Radic Biol Med. 2012 Jul 1;53(1):122-8 - PubMed
  27. Neuro Endocrinol Lett. 2009;30(6):715-22 - PubMed
  28. Int Immunopharmacol. 2014 Jan;18(1):55-65 - PubMed
  29. Cell Biosci. 2013 Jun 10;3(1):26 - PubMed
  30. Gastroenterology. 1995 Oct;109(4):1249-56 - PubMed
  31. Cell. 2009 Jun 12;137(6):1062-75 - PubMed
  32. Dig Liver Dis. 2002 Jun;34(6):387-92 - PubMed
  33. Gastroenterology. 1991 Jan;100(1):203-11 - PubMed
  34. J Clin Invest. 1994 Dec;94(6):2183-92 - PubMed

Publication Types