Liver and apoptosis.
Apoptosis is an energy-requiring mechanism of cell death which is a physiological event in organ morphogenesis, clone selection of lymphoid cells and cell turnover, but also occurs in many pathological conditions. It is under genetic control, bcl-2 being the major apoptosis suppressing gene, while p53 and c-myc are apoptosis promoting genes. Other factors, such as the Fas/Fas1 system, the caspases cascade, cytokines and enzymes also play a role in determining apoptosis. The term apoptosis was introduced by Kerr to describe this type of death in ischaemic rat liver, and the same Councilman bodies are now considered an example of apoptotic death. Virus-infected hepatocytes bear Fas receptors and apoptosis is induced by binding to the Fas ligand which is expressed by activated T cells; this action is probably mediated by enzymes of the caspase family and/or by granzyme B. The Fas/Fas1 system is also involved in apoptosis occurring in chronic non suppurative destructive cholangitis, in transplant rejection and in other liver diseases, including neoplasms; in the latter Bcl-2 protein and mutations of p53 also seem to play an important role. Cytokines are also frequently involved. Toxins like alcohol probably induce apoptosis by producing active oxidants. Whether aging enhances apopstosis in liver is still controversial. Although many molecular mechanisms have been suggested to be involved the switch on/off of apoptosis is still poorly understood and will be a matter of further investigations.
Valente
M
M
Department of Pathology, University of Padua Medical School, Italy. mvalente@uxl.unipd.it
Calabrese
F
F
D000375:Aging / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D019254:Genes, bcl-2 / Q000235:genetics; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008107:Liver Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D051381:Rats; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D019014:fas Receptor / Q000235:genetics
D016207:Cytokines; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor