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Role of Apoptosis in Liver Diseases

  • Hayato Hikita
  • Tetsuo TakeharaEmail author
Chapter

Abstract

In the livers of patients with various chronic hepatic diseases, including viral hepatitis, alcoholic liver disease and non-alcoholic fatty liver disease, hepatocyte apoptosis is frequently detected. Hepatocyte apoptosis is regulated by pro-apoptotic and anti-apoptotic bcl-2 family proteins. Among the anti-apoptotic proteins, Bcl-xL and Mcl-1 collaborate to prevent the activation of the mitochondrial apoptotic pathway and to maintain hepatocyte homeostasis. Hepatocyte apoptosis is directly linked with the progression of liver diseases, including liver fibrogenesis and liver tumorigenesis. The regulation of hepatocyte apoptosis is one of the therapeutic strategies to prevent the progression of chronic liver diseases. In in vitro and in vivo mouse models of non-alcoholic fatty liver disease, hepatocyte autophagy is suppressed by Rubicon overexpression leading to an increase in ER stress and hepatocyte apoptosis. Rubicon inhibition ameliorates the increase in ER stress and hepatocyte apoptosis. Rubicon overexpression is also observed in the livers of patients with non-alcoholic fatty liver disease. Rubicon-targeted improvement of hepatocyte autophagy may thus be a new therapeutic strategy for patients with non-alcoholic fatty liver disease. Therefore, further mechanistic insights into how hepatocyte apoptosis is executed in patients with different chronic liver diseases may lead to the discovery of new therapeutic strategies that can suppress the progression of chronic liver diseases.

Keywords

Bcl-2 family proteins Bcl-xL Mcl-1 Chronic hepatitis Oxidative stress Liver tumorigenesis Rubicon Autophagy Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis 

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Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Osaka University, Graduate School of MedicineSuitaJapan

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