Apoptosis and the liver

Regulation of the homeostatic balance between cell proliferation and programed cell death, apoptosis, is essential for development and maintenance of multicellular organisms. Apoptosis is a genetically and evolutionarily highly conserved process. Analysis of the molecular mechanisms of apoptosis has led to a better understanding of many human diseases. Notably in cancer; but also in infectious or autoimmune disease a deficiency in apoptosis is one of the key events in pathophysiology. On the other hand over-efficient apoptosis, as observed in fulminant liver failure, may be equally harmful for the organism indicating that a tight regulation of the nl,apoptotic machinery is essential for survival. The execution of apoptosis may be initiated by many different signals, either from within or outside the cell involving ligand-receptor interactions, as has been shown for Fas/Fas-liguand, TNF-alpha/TNF-receptor or TGF-beta/TGF-receptor; or potentially by more unspecific signals such as ceramide or DNA damage. During the modulation phase of apoptosis many differ mt genes such as p53, c-myc or Bcl-2/Bax have been shown to able to shift the balance either to cell survival or cell death. (C) 2000 Academic Press.