Further Characterization of a Rat Hepatoma‐Derived Aldose‐Reductase‐Like Protein

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Abstract
A protein detected in N‐methyl‐N‐nitrosourea‐initiated rat hepatomas by two‐dimensional electrophoresis at 35 kDd/pI 7.4 was identified in a previous study by internal amino acid micro sequencing as an aldose‐reductase‐like protein [Zeindl‐Eberhart, E., Jungblut, P. R., Otto, A. & Rabes, H. M. (1994) Identification of tumor‐associated protein variants during rat hepatocarcinogenesis, J. Biol. Chem. 269, 14589–145941. 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 rat lens aldose reductase after amino acid sequencing and 80% sequence identity to the rat‐hepatoma‐derived aldose‐reductase‐like protein. This 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 various 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 found preferentially in hepatomas and in embryonic liver. Though different in organ expression, an identical response was found for both proteins after stimulation with fibroblast growth factor‐1 and after exposure to increased glucose concentrations. Since rat hepatoma‐derived aldose‐reductase‐like protein is expressed in embryonic, but not in adult liver, it is assumed that it is expressed in hepatomas as a functionally active embryonal type of aldose reductase during hepatocarcinogenesis. Immunohistochemistry revealed that the hepatoma‐derived aldose‐reductase‐like protein is expressed already in the preneoplastic stage of hepatocarcinogenesis and might potentially serve as a marker enzyme in early hepatic neoplasia.

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