Summary
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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References
Calam DH, Waley SG (1963) Acidic peptides of the lens. 8:S-(α β-dicarboxyethyl)glutathione. Biochem J 86:226–231
Edwards AM, Lucas CM (1985) Phenobarbital and some other liver tumor promoters stimulate DNA synthesis in cultured rat hepatocytes. Biochem Biophys Res Commun 131: 103–108
Hasegawa K, Watanabe K, Koga M (1982) Induction of mitosis in primary cultures of adult rat hepatocytes under serum-free conditions. Biochem Biophys Res Commun 104:259–265
Katagiri K, Suzuki T, Monden Y, Jinno S, Hirayama Y, Yamaki T, Yano M (1989) Stimulation of DNA synthesis in adult rat hepatocytes in primary culture by a new hepatocyte growth accelerator: KZ-1026. Tissue Culture Res Commun 7:1–8
Katsuta H, Takaoka T (1976) Improved synthetic media suitable for tissue culture of various mammalian cells. Methods Cell Biol 14:145–158
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with Folin phenol reagent. J Biol Chem 193:265–275
McGowan JA, Strain AJ, Bucher NLR (1981) DNA synthesis in primary cultures of adult rat hepatocytes in a defined medium: effects of epidermal growth factor, insulin, glucagon, and cyclic-AMP. J Cell Physiol 108:353–363
Michalopoulos G, Cianciulli HD, Novotny AR, Kligerman AD, Strom SC, Jirtle RL (1982) Liver regeneration studies with rat hepatocytes in primary culture. Cancer Res 42: 4673–4682
Miyazaki M, Tsunashima M, Wahid S, Miyano K, Sato J (1984) Comparison of cytologic and biochemical properties between liver cells isolated from adult rats by trypsin perfusion and those isolated by collagenase perfusion. Res Exp Med 184:191–204
Miyazaki M, Handa Y, Oda M, Yabe T, Miyano K, Sato J (1985) Long-term survival of functional hepatocytes from adult rat in the presence of phenobarbital in primary culture. Exp Cell Res 159:176–190
Miyazaki M, Suzuki Y, Sato J (1988) A method for rapid preparation of single-cell suspensions from rat hepatocyte primary cultures on collagen substratum and the mechanism of cell dissociation. Acta Med Okayama 42:351–354
Nakamura T, Tomita Y, Ichihara A (1983) Density-dependent growth control of adult rat hepatocytes in primary culture. J Biochem 94:1029–1035
Nakamura T, Teramoto H, Tomita Y, Ichihara A (1984) l-Proline is an essential amino acid for hepatocyte growth in culture. Biochem Biophys Res Commun 122:884–891
Nakamura T, Nawa K, Ichihara A (1984) Partial purification and characterization of hepatocyte growth factor from serum of hepatectomized rats. Biochem Biophys Res Commun 122:1450–1459
Nakamura T, Teramoto H, Ichihara A (1986) Purification and characterization of a growth factor from rat platelets for mature parenchymal hepatocytes in primary culture. Proc Natl Acad Sci USA 83:6489–6493
Paul D, Piasecki A (1984) Rat platelets contain growth factor(s) distinct from PDGF which stimulate DNA synthesis in primary adult rat hepatocyte cultures. Exp Cell Res 154:95–100
Richman RA, Claus TH, Pilkis SJ, Friedman DL (1976) Hormonal stimulation of DNA synthesis in primary cultures of adult rat hepatocytes. Proc Natl Acad Sci USA 73:3589–3593
Russell WE, McGowan JA, Bucher NLR (1984) Partial characterization of a hepatocyte growth factor from rat platelets. J Cell Physiol 119:183–192
Sawada N, Staecker JL, Pitot HC (1987) Effects of tumor-promoting agents 12-O-tetradecanoylphorbol-13-acetate and phenobarbital on DNA synthesis of rat hepatocytes in primary culture. Cancer Res 47:5665–5671
Tomomura A, Sawada N, Sattler GL, Kleinman HK, Pitot HC (1987) The control of DNA synthesis in primary cultures of hepatocytes from adult and young rats: interactions of extracellular matrix components, epidermal growth factor, and the cell cycle. J Cell Physiol 130:221–227
Tsuboi S, Uda N, Ikeda M, Hirota K, Ohmori S (1984) S-(1,2-Dicarboxyethyl)glutathione and S-(1,2-dicarboxyethyl) l-cysteine in lens. J Clin Chem Clin Biochem 22:285–290
Tsuboi S, Kobayashi M, Nanba M, Imaoka S, Ohmori S (1990) S-(1,2-Dicarboxyethyl)-glutathione and activity for its synthesis in rat tissues. J Biochem 107:539–545
Tsuboi S, Ohnaka M, Ohmori S, Sakaue T, Ogata K, Itano T, Hatase O (1990) Inhibition of platelet aggregation by S-(1,2-dicarboxyethyl)-glutathione, intrinsic tripeptide in liver, heart, and lens. Arch Biochem Biophys 279:146–150
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Miyazaki, M., Bai, L., Tsuboi, S. et al. Enhancing effect of S-(1,2-dicarboxyethyl)glutathione on epidermal growth factor-stimulated DNA synthesis in primary cultures of adult rat hepatocytes. Res. Exp. Med. 190, 381–387 (1990). https://doi.org/10.1007/BF00000044
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DOI: https://doi.org/10.1007/BF00000044