FURTHER CHARACTERIZATION OF A RAT HEPATOMA-DERIVED ALDOSE-REDUCTASE-LIKE PROTEIN - ORGAN DISTRIBUTION AND MODULATION IN-VITRO

A protein detected in N-methyl-N-nitrosourea-initiated rat hepatomas b y two-dimensional electrophoresis at 35 kDa/pI 7.4 was identified in a previous study by internal amino acid micro sequencing as an aldose-r eductase-like protein [Zeindl-Eberhart, E., Juneblut. P. R., Otto, A. & Rabes, H. M. (1994) Identification of tumor-associated protein varia nts during rat hepatocarcinogenesis, J. Biol. Chem. 269, 14589-14594]. Two-dimensional electrophoresis of rat lens proteins revealed a spot at 37 kDa/pI 6.8 that showed a high degree of identity (98.5%) with ra t lens aldose reductase after amino acid sequencing and 80% sequence i dentity to the rat-hepatoma-derived aldose-reductase-like protein. Thi s suggests that hepatoma-derived aldose-reductase-like protein and rat lens aldose reductase are related proteins encoded by different genes . A different expression profile of these proteins was found in variou s rat organs. Rat lens aldose reductase is present, in addition to in lens, in heart, brain, muscle, lung, duodenum, kidney, spleen and bone marrow, while the hepatoma-derived aldose-reductase-like protein is f ound preferentially in hepatomas and in embryonic liver. Though differ ent in organ expression, an identical response was found for both prot eins after stimulation with fibroblast growth factor-1 and after expos ure to increased glucose concentrations. Since rat hepatoma-derived al dose-reductase-like protein is expressed in embryonic, but not in adul t liver, it is assumed that it is expressed in hepatomas as a function ally active embryonal type of aldose reductase during hepatocarcinogen esis. Immunohistochemistry revealed that the hepatoma-derived aldose-r eductase-like protein is expressed already in the preneoplastic stage of hepatocarcinogenesis and might potentially serve as a marker enzyme in early hepatic neoplasia.