Effects of melatonin on proliferation, oxidative stress and Cx32 gap junction protein expression in primary cultures of adult rat hepatocytes.
Melatonin has antiproliferative and antioxidant effects on cells in vivo and in vitro. Gap junctions mediate the communication between adjacent cells and are closely related to cellular growth and oxidative stress. We previously reported that 2% dimethylsulfoxide (DMSO) which has antiproliferative and antioxidative effects on hepatocytes, induces connexin 32 (Cx32) gap junction protein in primary cultures of adult rat hepatocytes. In the present study, we have examined the effects of melatonin on proliferation, oxidant stress and Cx32 gap junction protein expression in the cultured rat hepatocytes as compared to 2% DMSO treatment. 10(-2) M melatonin significantly inhibited the proliferation and the oxidative stress of the cells, and markedly induced Cx32 gap junction protein expression and gap junctional intercellular communication (GJIC). These effects of 10(-2) M melatonin treatment were not due to cytotoxicity to the cultured rat hepatocytes and they were as strong as those of 2% DMSO treatment. These results suggested that melatonin might be a useful substance to maintain the functions of the hepatocytes in vitro by modulating the levels of proliferation, oxidative stress and gap junction expression.
Kojima
T
T
Department of Pathology, Cancer Research Institute, Sapporo Medical University School of Medicine, Chuo-ku, Japan.
Mochizuki
C
C
Mitaka
T
T
Mochizuki
Y
Y
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D017630:Connexins / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D017629:Gap Junctions / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000097002:Gap Junction beta-1 Protein
D017630:Connexins; D008550:Melatonin; D000097002:Gap Junction beta-1 Protein