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鼠类醛酮还原酶家族 1 亚家族 B:鉴定 AKR1B8 为人类 AKR1B10 的同源物。

Murine aldo-keto reductase family 1 subfamily B: identification of AKR1B8 as an ortholog of human AKR1B10.

机构信息

Department of Medical Microbiology, Immunology and Cell Biology, Simmons Cooper Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL 62794, USA.

出版信息

Biol Chem. 2010 Dec;391(12):1371-8. doi: 10.1515/BC.2010.144.

Abstract

Aldo-keto reductase family 1 member B10 (AKR1B10), over-expressed in multiple human cancers, might be implicated in cancer development and progression via detoxifying cytotoxic carbonyls and regulating fatty acid synthesis. In the present study, we investigated the ortholog of AKR1B10 in mice, an ideal modeling organism greatly contributing to human disease investigations. In the mouse, there are three aldo-keto reductase family 1 subfamily B (AKR1B) members, i.e., AKR1B3, AKR1B7, and AKR1B8. Among them, AKR1B8 has the highest similarity to human AKR1B10 in terms of amino acid sequence, computer-modeled structures, substrate spectra and specificity, and tissue distribution. More importantly, similar to human AKR1B10, mouse AKR1B8 associates with murine acetyl-CoA carboxylase-α and mediates fatty acid synthesis in colon cancer cells. Taken together, our data suggest that murine AKR1B8 is the ortholog of human AKR1B10.

摘要

醛酮还原酶家族 1 成员 B10(AKR1B10)在多种人类癌症中过度表达,可能通过解毒细胞毒性羰基化合物和调节脂肪酸合成来参与癌症的发生和发展。在本研究中,我们研究了 AKR1B10 在小鼠中的同源物,作为一种对人类疾病研究有重大贡献的理想建模生物。在小鼠中,有三个醛酮还原酶家族 1 亚家族 B(AKR1B)成员,即 AKR1B3、AKR1B7 和 AKR1B8。其中,AKR1B8 在氨基酸序列、计算机建模结构、底物谱和特异性以及组织分布方面与人类 AKR1B10 具有最高的相似性。更重要的是,与人类 AKR1B10 相似,小鼠 AKR1B8 与鼠乙酰辅酶 A 羧化酶-α结合,并在结肠癌细胞中介导脂肪酸合成。综上所述,我们的数据表明,小鼠 AKR1B8 是人类 AKR1B10 的同源物。

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