Different functions between human monomeric carbonyl reductase 3 and carbonyl reductase 1
Different functions between human monomeric carbonyl reductase 3 and carbonyl reductase 1
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DOI：
10.1007/s11010-008-9794-5
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发表时间：
2008-08-01
影响因子：
4.3
通讯作者：
Terada, Tomoyuki
中科院分区：
文献类型：
--
作者：
Miura, Takeshi;Nishinaka, Toru;Terada, Tomoyuki
单体羰基还原酶（CBRs）是催化许多内源性和外源性羰基化合物还原的酶，包括类固醇和前列腺素。人类基因组中存在cbr1和cbr3两个单体CBR基因，它们在氨基酸序列上具有高度同源性。人CBR1 （hCBR1）被称为前列腺素9-酮还原酶和15-羟基脱氢酶，通过调节前列腺素代谢调节癌细胞转移。然而，关于人CBR3 （hCBR3）的分子和酶特性的信息很少。本研究证实了hCBR3的组织和细胞定位以及催化活性。半定量PCR显示hCBR3普遍存在，但与hCBR1相比表达较低。细菌表达的hCBR3对甲萘醌、4-苯甲酰吡啶和4-硝基苯甲醛的催化活性有限。当检测过表达cbr的HEK293细胞的细胞裂解物时，也得到了类似的结果。此外，hCBR3的前列腺素9-酮还原酶和15-羟基脱氢酶活性均不显著。免疫荧光染色显示，异位表达的hCBR3蛋白定位于HEK293细胞的细胞质中。这些结果表明hCBR3和hCBR1具有不同的生理作用。这项研究扩大了我们对两种单体hCBRs与前列腺素代谢之间关系的理解。
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.