Abstract

A tripeptide S-(1,2-dicarboxyethyl)glutathione (DCE-GS) has been reported to be present in the lens, liver, and heart. Effects of DCE-GS and its derivatives and analogues on hepatocyte deoxyribonucleic acid (DNA) synthesis were examined using primary cultures of adult-rat hepatocytes. DCE-GS alone had no effect on DNA synthesis of hepatocytes. However, when DCE-GS was added with epidermal growth factor (EGF), the tripeptide effectively enhanced EGF-stimulated DNA synthesis of hepatocytes under the culture conditions of low cell density, but not high cell density. On the other hand, some esters and amides of DCE-GS and DCE-GS analogues showed a suppressive effect on DNA synthesis of hepatocytes in the absence of EGF. The derivatives and analogues together with EGF had no effect or rather a suppressive effect on stimulation of hepatocyte DNA synthesis by EGF. Therefore, the two carboxy groups in the substituent probably play an important role in the stimulative activity of DCE-GS. In addition, it seems likely that one of in vivo physiological roles of DCE-GS is related to liver regeneration.

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