Regulation of genes for inducible nitric oxide synthase and urea cycle enzymes in rat liver in endotoxin shock

被引:40
作者
Tabuchi, S
Gotoh, T
Miyanaka, K
Tomita, K
Mori, M
机构
[1] Kumamoto Univ, Sch Med, Dept Mol Genet, Kumamoto 8600811, Japan
[2] Kumamoto Univ, Sch Med, Dept Internal Med 3, Kumamoto 8600811, Japan
关键词
D O I
10.1006/bbrc.2000.2105
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Arginine is an intermediate of the urea cycle in the liver. It is synthesized by the first four enzymes of the cycle, carbamylphosphate synthetase I, ornithine transcarbamylase, argininosuccinate synthetase, and argininosuccinate lyase, and is hydrolyzed to urea and ornithine by arginase I, forming the cycle. In endotoxemia shock, inducible nitric oxide (NO) synthase (iNOS) is induced in hepatocytes and arginine is utilized for NO production. Regulation of the genes for iNOS and the urea cycle enzymes was studied using lipopolysaccharide (LPS)-treated rat livers. When rats were injected intraperitoneally with LPS, iNOS mRNA was markedly induced. Cationic amino acid transporter-2 and C/EBP beta mRNAs were also highly increased. In contrast, mRNAs for all the urea cycle enzymes except ornithine transcarbamylase were gradually decreased and reached 16-28% of controls at 12 h. However, all these enzymes remained unchanged at protein level up to 24 h. In light of these results, we suggest that synthesis of urea cycle enzymes is downregulated and that the protein synthetic capacity is directed to synthesis of proteins required for defense against endotoxemia. (C) 2000 Academic Press.
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页码:221 / 224
页数:4
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