Context Dependent Role of P53 Up-Regulated Modulator of Apoptosis (Puma) During Liver Degeneration and Regeneration

Abstract

Hepatocytes are susceptible to injury due to its contribution in xenobiotic metabolism including drugs and alcohol, fatty acid metabolism and enterohepatic circulation of bile acids and hepato tropic viruses. On the other hand regeneration of hepatocytes is well-studied phenomenon essential for maintenance of its volume during chronic liver injury as well as acute restoration of liver volume after resection. During chronic and acute insult of liver apoptosis and necrosis are the most widely documented forms of hepatocyte cell death. Experimental evidence also demonstrates that apoptosis and cell proliferation are closely linked and many proteins that can induce cell death are, in fact, components of the cell division cycle. Apoptosis is crucial for sustain tissue homeostasis and its circumvention is assumed as a hallmark of cancer. Conversely, there are several evidences also support the contribution of pro-apoptotic Bcl-2 family members in development of liver cancer. They also play vital role during liver regeneration induced by partial hepatectomy, a well characterized in vivo model of cell cycle progression. Here we discuss the context dependent role of specifically one BH3 only group of Bcl-2 family member, Puma during hepatic degeneration and regeneration. Up regulation and down regulation of this specific protein is vital for carcinogenesis as well as hepatic regeneration. The expression levels of Puma contributing to hepatocyte injuries, hepatic proliferation and progression of malignancies are also reflected in the context of potential therapeutic strategies.