Aldo-keto reductase family 1 B10 protein detoxifies dietary and lipid-derived alpha, beta-unsaturated carbonyls at physiological levels.
Aldo-keto reductase family 1 B10 protein detoxifies dietary and lipid-derived alpha, beta-unsaturated carbonyls at physiological levels.
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DOI：
10.1016/j.bbrc.2009.06.123
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发表时间：
2009-09-18
影响因子：
3.1
通讯作者：
Cao D
中科院分区：
文献类型：
--
作者：
Zhong L;Liu Z;Yan R;Johnson S;Zhao Y;Fang X;Cao D
α，β-不饱和羰基化合物是人类每天接触的高活性诱变剂和致癌物。这项研究表明，醛酮还原酶家族1成员B10（AKR 1B 10）是解毒膳食和脂质衍生的不饱和羰基化合物的关键蛋白质。纯化的AKR 1B 10重组蛋白有效催化还原为毒性较低的醇形式的巴豆醛（0.90 µM）、4-羟基壬烯醛（HNE）（0.10 µM）、反式-2-己醛（0.10 µM）和反式-2，4-己二烯醛（0.05 µM），浓度等于或低于生理暴露。在293 T细胞中异位表达的AKR 1B 10通过转化为1，4-二羟基壬烯立即消除1 μ M（亚毒性）或5 μM（毒性）的HNE，保护细胞免受HNE毒性。AKR 1B 10蛋白对谷胱甘肽结合的羰基也表现出强的酶活性。综上所述，我们的研究结果表明，AKR 1B 10在肠道中特异性表达，在保护宿主细胞免受饮食和脂质来源的细胞毒性羰基化合物的侵害方面具有重要的生理学意义。
Alpha, beta-unsaturated carbonyls are highly reactive mutagens and carcinogens to which humans are exposed on a daily basis. This study demonstrates that aldo-keto reductase family 1 member B10 (AKR1B10) is a critical protein in detoxifying dietary and lipid-derived unsaturated carbonyls. Purified AKR1B10 recombinant protein efficiently catalyzed the reduction to less toxic alcohol forms of crotonaldehyde at 0.90 µM, 4-hydroxynonenal (HNE) at 0.10 µM, trans-2-hexanal at 0.10 µM, and trans-2, 4-hexadienal at 0.05 µM, the concentrations at or lower than physiological exposures. Ectopically expressed AKR1B10 in 293T cells eliminated immediately HNE at 1 (subtoxic) or 5 µM (toxic) by converting to 1, 4-dihydroxynonene, protecting the cells from HNE toxicity. AKR1B10 protein also showed strong enzymatic activity toward glutathione-conjugated carbonyls. Taken together, our study results suggest that AKR1B10 specifically expressed in the intestine is physiologically important in protecting the host cell against dietary and lipid-derived cytotoxic carbonyls.
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影响因子：
56.9
作者：
AMES, BN
通讯作者：
AMES, BN
影响因子：
2.3
作者：
Lee, KWY;Ko, BCB;Chung, SSM
通讯作者：
Chung, SSM
人醛酮还原酶 AKR1B10 氧化 PAH 反式二氢二醇。
影响因子：
4.1
作者：
Quinn, Amy M.;Harvey, Ronald G.;Penning, Trevor M.
通讯作者：
Penning, Trevor M.
影响因子：
11.5
作者：
Fukumoto, S;Yamauchi, N;Aburatani, H
通讯作者：
Aburatani, H
DOI：
10.1073/pnas.92.7.2780
发表时间：
1995-03-28
影响因子：
11.1
作者：
LEE, AYW;CHUNG, SK;CHUNG, SSM
通讯作者：
CHUNG, SSM