Y. Achouri et al., Role of cysteine in the dietary control of the expression of 3-phosphoglycerate dehydrogenase in rat liver, BIOCHEM J, 344, 1999, pp. 15-21
Shifting rats to a protein-free, carbohydrate-rich diet, although not starv
ation, resulted in the appearance of mRNA for, and activity of, 3-phosphogl
ycerate 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 sh and its complete disappearance within 24 h, followed by a
slower disappearance of the enzymic activity. Intraperitoneal administrati
on of cysteine or methionine to protein-starved rats decreased the mRNA by
50-60% after 8 h. However, the repeated administration of cysteine failed t
o 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 pl
us methionine but was still apparent in the presence of glucagon. Nuclear r
un-on experiments and analysis of the stability of the mRNA with 5,6-dichlo
robenzimidazole 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 he
patoma 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 g
lucagon and the positive effect of insulin.