Journal
CELL AND BIOSCIENCE
Volume 4, Issue -, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/2045-3701-4-47
Keywords
Autophagy; Bile acid; Cholestasis; Hepatocyte; Reactive oxygen species
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Funding
- Key Basic Research Project of China [2012CBA01303, 2011CB966200, 2010CB945600, 2011CB965100]
- Key project of National Natural Science Foundation of China [81030041]
- National Natural Science Foundation of China [31171321, 81101622, 81372330]
- Special Funds for National key Sci-Tech Sepcial Project of China [2012ZX10002-016, 2012ZX10002011-011]
- Shanghai Science and Technology Committee [10ZR1439600, 11ZR1449500]
- Shanghai Municipal Health Bureau [XYQ2011044]
- Science Fund for Creative Research Groups, NSFC, China [81221061]
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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.
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