Autophagy in liver diseases

作者:Rautou Pierre Emmanuel*; Mansouri Abdellah; Lebrec Didier; Durand Francois; Valla Dominique; Moreau Richard
来源:Journal of Hepatology, 2010, 53(6): 1123-1134.
DOI:10.1016/j.jhep.2010.07.006

摘要

Autophagy or cellular self-digestion is a cellular pathway crucial for development differentiation survival and homeostasis Its implication in human diseases has been highlighted during the last decade Recent data show that autophagy is involved in major fields of hepatology In liver ischemia reperfusion injury autophagy mainly has a prosurvival activity allowing the cell for coping with nutrient starvation and anoxia During hepatitis B or C infection autophagy is also increased but subverted by viruses for their own benefit In hepatocellular carcinoma the autophagy level is decreased In this context autophagy has an anti-tumor role and therapeutic strategies increasing autophagy as rapamycin have a beneficial effect in patients Moreover in hepatocellular carcinoma Beclin-1 level an autophagy protein has a prognostic significance In alpha-1-antitrypsin deficiency the aggregation-prone ATZ protein accumulates in the endoplasmic reticulum This activates the autophagic response which aims at degrading mutant ATZ Some FDA-approved drugs which enhance autophagy and the disposal of aggregation-prone proteins may be useful in alpha-1-antitrypsin deficiency Following alcohol consumption autophagy is decreased in liver cells likely due to a decrease in intracellular 5'-AMP-activated protein kinase (AMPk) and due to an alteration in vesicle transport in hepatocytes This decrease in autophagy contributes to the formation of Mallory-Denk bodies and to liver cell death Hepatic

  • 出版日期2010-12