Regulation of genes for inducible nitric oxide synthase and urea cycle enzymes in rat liver in endotoxin shock.
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/EBPbeta 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.
Tabuchi
S
S
Department of Molecular Genetics, Kumamoto University School of Medicine, Kumamoto, 860-0811, Japan.
Gotoh
T
T
Miyanaka
K
K
Tomita
K
K
Mori
M
M
D026923:Amino Acid Transport Systems, Basic; D000818:Animals; D001123:Argininosuccinate Lyase / Q000235:genetics / Q000378:metabolism; D001124:Argininosuccinate Synthase / Q000235:genetics / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins; D002222:Carbamoyl-Phosphate Synthase (Ammonia) / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D009687:Nuclear Proteins / Q000235:genetics; D009954:Ornithine Carbamoyltransferase / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D014508:Urea / Q000378:metabolism*
D026923:Amino Acid Transport Systems, Basic; D022762:CCAAT-Enhancer-Binding Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014508:Urea; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D009954:Ornithine Carbamoyltransferase; D001123:Argininosuccinate Lyase; D002222:Carbamoyl-Phosphate Synthase (Ammonia); D001124:Argininosuccinate Synthase