Nitric oxide production and its contribution to hepatocyte proliferation in normal juvenile rats.
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.
Inukai
Naoto
N
Graduate School of Veterinary Medicine, Azabu University, Kanagawa, Japan.
Uchida
Mayuko
M
Miyazaki
Yoko
Y
Suzuki
Takehito
T
Yoshikawa
Hiroshi
H
Tanaka
Kazuaki
K
Morita
Hidetoshi
H
Takizawa
Tatsuya
T
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
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