Role of cysteine in the dietary control of the expression of 3-phosphoglycerate dehydrogenase in rat liver.
Shifting rats to a protein-free, carbohydrate-rich diet, although not starvation, resulted in the appearance of mRNA for, and activity of, 3-phosphoglycerate dehydrogenase (3-PGDH) in liver as well as in a marked decrease in plasma cystine concentration. Refeeding with protein caused a 50% decrease in the mRNA in 8 h and its complete disappearance within 24 h, followed by a slower disappearance of the enzymic activity. Intraperitoneal administration of cysteine or methionine to protein-starved rats decreased the mRNA by 50-60% after 8 h. However, the repeated administration of cysteine failed to cause the complete disappearance of this mRNA in 24 h. In hepatocytes in primary culture, cysteine plus methionine and glucagon had, independently, an approx. 4-fold inhibitory effect on the abundance of the 3-PGDH mRNA and caused its almost complete disappearance when tested together. Insulin had an approx. 2-fold stimulatory effect, which was antagonized by cysteine plus methionine but was still apparent in the presence of glucagon. Nuclear run-on experiments and analysis of the stability of the mRNA with 5,6-dichlorobenzimidazole riboside, an inhibitor of RNA polymerase II, suggested that the effect of cysteine plus methionine was due to destabilization of the mRNA, whereas the effect of glucagon was exerted on transcription. Cysteine, but not methionine, inhibited the accumulation of 3-PGDH mRNA in FTO2B hepatoma cells. In conclusion, the dietary control of the expression of the 3-PGDH gene in liver seems to involve the negative effects of cysteine and glucagon and the positive effect of insulin.
Achouri
Y
Y
Laboratory of Physiological Chemistry, ICP, Université Catholique de Louvain, BCHM 7539, Avenue Hippocrate 75, B-1200 Brussels, Belgium.
Robbi
M
M
Van Schaftingen
E
E
D000596:Amino Acids / Q000097:blood / Q000494:pharmacology; D000818:Animals; D002237:Carbohydrate Dehydrogenases / Q000235:genetics*; D003545:Cysteine / Q000494:pharmacology*; D004032:Diet; D004044:Dietary Proteins / Q000008:administration & dosage; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005934:Glucagon / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000201:enzymology / Q000235:genetics; D008297:Male; D008715:Methionine / Q000494:pharmacology; D050543:Phosphoglycerate Dehydrogenase; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000596:Amino Acids; D004044:Dietary Proteins; D007328:Insulin; D012333:RNA, Messenger; D005934:Glucagon; D008715:Methionine; D002237:Carbohydrate Dehydrogenases; D050543:Phosphoglycerate Dehydrogenase; D003545:Cysteine