Different functions between human monomeric carbonyl reductase 3 and carbonyl reductase 1.
Monomeric carbonyl reductases (CBRs) are enzymes that catalyze the reduction of many endogenous and xenobiotic carbonyl compounds, including steroids and prostaglandins. There are two monomeric CBR genes in the human genome, cbr1 and cbr3, which exhibit high homology in their amino acid sequences. Human CBR1 (hCBR1) is known as prostaglandin 9-keto reductase and 15-hydroxy dehydrogenase, and regulates the metastasis of cancer cells through the regulation of prostaglandin metabolism. However, there is little information concerning the molecular and enzymatic characteristics of human CBR3 (hCBR3). The present study demonstrated the tissue and cellular localization, and catalytic activity of hCBR3. Semi-quantitative PCR revealed the ubiquitous but lower expression of hCBR3 compared with that of hCBR1. Bacterially expressed hCBR3 exhibited limited catalytic activity toward menadione, 4-benzoylpyridine, and 4-nitrobenzaldehyde. Similar results were obtained when the cell lysates of CBR-overexpressing HEK293 cells were examined. Additionally, neither the prostaglandin 9-keto reductase nor the 15-hydroxy dehydrogenase activities of hCBR3 were significant. Immunofluorescence staining revealed that ectopically expressed hCBR3 proteins were localized in the cytosol of HEK293 cells. These results suggested that hCBR3 and hCBR1 play distinct physiological roles. This study expands our understanding of the relationship between the two monomeric hCBRs and prostaglandin metabolism.
Miura
Takeshi
T
Laboratory of Biochemistry, Faculty of Pharmacy, Osaka Ohtani University, Nishikiori-kita, Tondabayashi, Osaka, Japan. miurat@osaka-ohtani.ac.jp
Nishinaka
Toru
T
Terada
Tomoyuki
T
D000429:Alcohol Oxidoreductases / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D002384:Catalysis; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004926:Escherichia coli; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D011453:Prostaglandins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D018076:DNA, Complementary; D011453:Prostaglandins; D012333:RNA, Messenger; D000429:Alcohol Oxidoreductases; C531129:CBR1 protein, human; C531130:CBR3 protein, human