Disease relevance of Cdo1

• Rat liver CDO was cloned and expressed in Escherichia coli as a 26.8-kDa N-terminal fusion protein bearing a polyhistidine tag [1].
• CDO mRNA was also detected in human hepatoblastoma HepG2 cells [2].

High impact information on Cdo1

• Kinetic studies showed that the recombinant enzyme displayed a K(m) value of 2.5 +/- 0.4 mm at pH 7.5 and 37 degrees C. The enzyme was shown to be specific for l-cysteine oxidation, whereas homocysteine inhibited CDO activity [1].
• Cysteine dioxygenase (CDO, EC 1.13.11.20) catalyzes the oxidation of cysteine to cysteine sulfinic acid, which is the first major step in cysteine catabolism in mammalian tissues [1].
• Taurine is supplied to the body by dietary ingestion as well as by de novo synthesis; it is anabolized by cysteine dioxygenase (CDO), which is abundantly expressed in liver and white adipose tissue [3].
• In high-fat diet-induced and/or genetically obese mice, a decrease in the blood taurine concentration was observed along with a decrease in CDO expression in adipose tissue but not in liver [3].
• In astrocytes exposed to a hyperosmotic medium the TauT mRNA level increased, whereas the CDO and CSD mRNA levels were not significantly altered [4].

Biological context of Cdo1

• Cysteine, rather than a precursor or metabolite of cysteine, appears to mediate the upregulation of cysteine dioxygenase (CDO) and the downregulation of glutamate cysteine ligase (GCL) in cultured primary rat hepatocytes [5].
• The CDO gene spanned about 15 kb, and comprised 5 exons [6].
• We have investigated the gene expression of the taurine transporter (TauT) and the taurine biosynthetic enzymes, cysteine dioxygenase (CDO) and cysteine sulfinate decarboxylase (CSD), in astrocyte primary cultures in relationship to cell taurine content [4].
• Taken together, these results suggest that cysteine itself is an important cellular signal for upregulation of CDO and downregulation of GCS [7].
• The structural similarities between the amino acid L-cysteine and SCMC have raised the possibility that cysteine dioxygenase (CDO) may be responsible for this biotransformation reaction [8].

Anatomical context of Cdo1

• Similar results were observed for degradation of recombinant CDO expressed in human heptocarcinoma cells cultured in cysteine-deficient or cysteine-supplemented medium [9].
• CDO protein and mRNA was localised solely to the neurones of the brain, including the pyramidal cells of the hippocampus and the Purkinje cells of the cerebellum [10].
• Significant expression of the CDO gene was detected in the liver, lung, and kidney, but not skeletal muscle [11].
• Its expression in the kidney tubules, the major site of sulphation in the kidney, suggests that CDO in the kidney may play a role in both xenobiotic metabolism and sodium and water homeostasis [12].
• The liver beta-carotene content and its accumulation rate were lower in the mid-level dietary fat groups (10 g fat/100 g diet). beta-carotene 15,15'-dioxygenase (CDO) activity in the small intestine increased in the mid-level dietary protein groups, which resulted in an increase in the content of liver retinol converted from dietary beta-carotene [13].

Associations of Cdo1 with chemical compounds

• However, similar experiments in intact rats have not been performed to confirm in vivo that changes in hepatic cysteine levels are associated with the regulation of CDO or GCL activity [5].
• Finally, by a combination of in vitro hepatocyte culture and in vivo whole animal studies, we were able to attribute the changes in CDO stability specifically to cysteine rather than the metabolite 2-mercaptoethylamine (cysteamine) [14].
• CONCLUSIONS: These results suggest that the 68 kDa Type II is the predominant isoform in vitro and in vivo and that its centrilobular localisation may allow CDO to initiate the production of sulphate and taurine for Phase II conjugation in the liver [15].
• Distribution was found to be centrilobular and did not alter when CDO was induced with cysteine or methionine; however, the intensity of staining increased, indicating an increase in the levels of CDO in that region [15].
• CDO- and CSD-mRNA remained unchanged, whereas AR-mRNA appeared increased only with the medium made hyperosmotic with sodium chloride [16].

Analytical, diagnostic and therapeutic context of Cdo1

• Northern blots of RNA from rat tissues revealed the highest CDO mRNA level in the liver [6].
• METHODS: Two novel anti-CDO antibodies raised against linear synthetic peptides corresponding to two distinct epitopes on the 22 kDa gene product of the CDO-I gene were used for immunohistochemistry and Western blotting [15].
• TauT, CDO, and CSD mRNA levels were determined through quantitative RT-PCR [4].
• Most studies have centred upon the hepatic form of the enzyme, but several studies have investigated brain CDO using activity assays and western blotting [10].
• Using either rabbit antibody raised against purified rat liver CDO or against purified recombinant his(6)-tagged CDO (r-his(6)-CDO) and using 15% (wt/vol) polyacrylamide for the SDS-PAGE, we consistently detected the approximately 25 kDa band, but never detected a approximately 68 kDa band, in rat liver, kidney, lung and brain [17].

References