title: Nitric oxide production and its contribution to hepatocyte proliferation in normal juvenile rats.
abstract: Nitric oxide (NO) has been reported as a key mediator in enhancing hepatocyte proliferation during liver regeneration. Juvenile hepatocytes have a strong ability to proliferate while still in their undifferentiated state but the mechanism of NO production and its contribution to hepatocyte proliferation are not yet fully understood. The present study was designed to investigate NO production in the normal liver and its contribution to hepatocyte proliferation in juvenile rats. Endogenous NO production was evaluated quantitatively using a spin trap followed by electron paramagnetic resonance spectroscopy with the Fe-N, N-diethyldithiocarbamate complex as an NO-trapping reagent in the rat liver. NO production in the liver significantly peaked at 3 weeks after birth, but NO synthase (NOS) 3 expression did not change between 2 to 5 weeks after birth, while NOS 1 and NOS 2 mRNA were not detected. Hepatocyte proliferation, measured by the incorporation of 5-bromo-2'-deoxyuridine into the DNA, was found to decline significantly when endogenous NO production was inhibited by the administration of the NOS inhibitor N(G)-nitro- (L)-arginine methyl ester. These findings indicate that endogenous NO production peaked at 3 weeks after birth and hepatocyte proliferation declined significantly when NO production was inhibited. Thus, this study provides a novel insight into the contribution of NO to hepatic growth and liver maturation in juveniles.
authors.affiliation: Graduate School of Veterinary Medicine, Azabu University, Kanagawa, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Inukai
authors.forename: Mayuko
authors.initials: M
authors.lastname: Uchida
authors.forename: Yoko
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Takehito
authors.initials: T
authors.lastname: Suzuki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yoshikawa
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Tanaka
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Morita
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Takizawa
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D002455:Cell Division; D017931:DNA Primers; D022781:Hepatocytes / Q000166:cytology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats / Q000254:growth & development / Q000378:metabolism; D012016:Reference Values
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D019331:NG-Nitroarginine Methyl Ester