The contribution of apoptosis to hepatocyte cell death after rat liver injury from the hepatotoxin galactosamine (GalN) was examined. Histologic evidence of diffuse hepatocyte apoptosis existed after GalN administration. Since apoptosis is an active form of cell death usually requiring new gene expression, it was determined whether genes associated with apoptosis were expressed following GalN liver injury. RP-8 and TRPM-2, two genes associated with apoptosis in other organs, were expressed in normal liver, and their mRNA levels increased after GalN injury. These genes were expressed in hepatocytes without any intralobular zonal gradient in expression. In contrast to GalN liver injury, RP-8 and TRPM-2 levels were unchanged during the purely proliferative response following rat partial hepatectomy. These data suggest that hepatocytes constitutively express the genetic program for apoptosis including the RP-8 and TRPM-2 genes. The ability of toxic liver injury to further stimulate expression of these genes may lead to apoptotic hepatocyte cell death.
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