Post-transcriptional regulation of cysteine dioxygenase in rat liver

Abstract

Changes in hepatic cysteine dioxygenase (CDO) activity in response to diet play a dominant role in regulation of cysteine catabolism and taurine synthesis. We have conducted several studies of the molecular regulation of CDO activity in rat liver and rat hepatocytes. Compared to levels observed in liver of rats fed a basal 10% casein diet, up to 180-fold higher levels of CDO activity and protein were observed in liver of rats fed diets that contained additional protein, complete amino acid mixture, methionine, or cystine5,6. Neither CDO activity nor CDO protein was induced by excess non-sulfur amino acids alone. Excess sulfur amino acids or protein did not significantly increase the concentration of hepatic CDO mRNA. Preliminary studies indicate that the polysome profile for association of CDO mRNA with polysomes is not altered by an increase in dietary protein level, suggesting that regulation may be posttranslational and possibly involve a decrease in the rate of CDO degradation. In primary cultures of rat hepatocytes, CDO mRNA, protein, and activity all virtually disappeared by 12 to 24 h of culture in standard medium14 whereas CDO protein, but not CDO mRNA, accumulated markedly between 12 and 24 h in hepatocytes cultured in medium with excess methionine or cyst(e)ine. These observations are also consistent with a limited role of transcriptional or translational regulation of CDO in response to diet.