Medicine of the Future in America

Liver cell death: Experimental models of hepatocyte apoptosis

There are a number of experimental models of hepatocyte apoptosis. Maybe the best known, and the one that has generated the widest interest, is the mouse model of massive liver apoptosis after the intraperitoneal injection of Fas antibodies. These antibodies bind to the Fas receptor and, instead of preventing its activation (as is the case for other antibodies such as the anti-TNF-a antibodies), they induce oligomerization of the Fas receptors and their consequent activation. When injected in vivo, this causes a rapid and massive liver injury characterized by overwhelming apoptosis. Other liver cells, such as endothelial cells, are also injured and there is some debate about the exact sequence of pathological events. Nevertheless, this model has been used to assess the capacity of agents to block hepatocyte apoptosis and has demonstrated the importance of the Fas system in this process.

TNF-a has been reported to induce hepatocyte apoptosis, but only in the presence of a transcriptional block (ie, an arrest of the synthesis of new messenger RNA). Models of inflammatory liver disease, in which TNF-a levels are increased, have been assessed for the presence of apoptosis. Liver injury induced by endotoxin, lipopolysaccharide or concanavalin have all been shown to exhibit hepatocyte apoptosis.

In vitro, hepatocyte apoptosis has been reproducibly induced by exposure to chenodeoxycholate, a known hepatotoxic bile salt, in concentrations similar to those found in cholestatic disorders. However, as is often the case with toxic agents, there is a concentration beyond which necrosis becomes more prominent than apoptosis. This well-known observation has not yet been explained. A recent report suggests that the degree of ATP availability determines the mode of cell death. You can find best pharmacy with finest quality medications available round the clock right now: all you need to do is buy ampicillin antibiotics at our here discovering the amazing opportunities you are being offered.

This entry was posted in Apoptosis and tagged Apoptosis, Hepatocyte, Liver diseases.
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