Expression of clusterin (testosterone-repressed prostate message-2) mRNA during growth and regeneration of rat liver.

Abstract

Clusterin has been used as a marker for apoptosis (often denoted "active" "or programmed" cell death) in the prostate, mammary gland and other solid organs. The protein is thought to be involved in membrane remodelling during separation of apoptotic cells from their vital neighbours and fragmentation into apoptotic bodies. In the present study, we have looked at the expression of clusterin during the growth and regression of rat liver induced by short term administration of the hepatomitogen, cyproterone acetate. The steady state level of clusterin mRNA, as measured by Northern and slot blot analysis, is low in control hepatocytes. Following administration of cyproterone acetate, the clusterin mRNA level is increased during both liver growth and regression. In situ hybridization reveals that clusterin is expressed in all hepatocytes, indicating that it is not confined to cell death by apoptosis. These results suggest that the gene product may be involved in maintaining membrane integrity, which is necessary during both mitosis and apoptosis. To determine whether clusterin mRNA is induced by membrane remodelling independent of either mitosis or apoptosis, we examined the expression of clusterin mRNA in the liver after a necrogenic dose of carbon tetrachloride. During the first 24-48 h of this time period, necrosis is the predominant form of cell death and liver regeneration starts after approximately 24 h. Elevated levels of clusterin mRNA are found as early as 12 h after carbon tetrachloride administration and persist for at least 72 h.(ABSTRACT TRUNCATED AT 250 WORDS)