Liver fatty acid binding protein and mitogenesis in transfected hepatoma cells.

Abstract

In recent years, multiple associations have linked induced cell proliferation (mitogenesis) of rat hepatocytes to liver fatty acid binding protein (L-FABP), a cytoplasmic 14 kDa protein previously termed Z protein. The protein was formerly thought to be solely a carrier of fatty acids in hepatocytes (reviewed 1–5). The first tie-in of L-FABP with hepatocyte multiplication came from the finding that the level of a protein, later identified as L-FABP, is increased markedly in the cytoplasm of hepatocytes during mitosis in normal and regenerating livers (6–8), and in contrast throughout the cell cycle in hyperplastic hepatocytes and hepatocarcinomas produced in rats by the genotoxic carcinogens, 2-acetylaminofluorene (AAF) and aminoazo dyes (6,9). In addition, L-FABP binds many potential modulators of cell growth, including four types of liver carcinogens, i.e. reactive metabolites of the two genotoxic carcinogens, AAF and aminoazo dyes, during hepatocarcinogenesis, and two classes of nongenotoxic carcinogenic peroxisomal proliferators (PP) that noncovalently bind to L-FABP in vivo. Also, L-FABP binds the essential fatty acids, linoleic acid and arachidonic acid; prostaglandin E1; growth modulatory hydroxy and hydroperoxy metabolites of arachidonic acid; growth inhibitory prostaglandins; mitogenic lysophosphatidic acids; lysophosphatidyl cholines; antiproliferative and anticancer selenium compound; retinyl palmitate; and heme. Lastly, L-FABP belongs to a protein family in which several members have been associated with the modulation of cell multiplication. [The relevant references are cited elsewhere (10–13)]. However, whether the bound ligands of L-FABP actually modulate mitogenesis of heaptocytes has been unknown.