Enhancing effect of S-(1,2-dicarboxyethyl)glutathione on epidermal growth factor-stimulated DNA synthesis in primary cultures of adult rat hepatocytes.
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.
Miyazaki
M
M
Department of Pathology, Okayama University Medical School, Japan.
Bai
L
L
Tsuboi
S
S
Ohmori
S
S
Ogata
K
K
Sato
J
J
Namba
M
M
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005978:Glutathione / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D013329:Structure-Activity Relationship
C041581:S-(1,2-dicarboxyethyl)glutathione; D004815:Epidermal Growth Factor; D004247:DNA; D005978:Glutathione