(S)-preferential detoxification of 4-hydroxy-2(E)-nonenal enantiomers by hepatic glutathione S-transferase isoforms in guinea-pigs and rats.
(S)-preferential detoxification of 4-hydroxy-2(E)-nonenal enantiomers by hepatic glutathione S-transferase isoforms in guinea-pigs and rats.
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DOI：
10.1042/bj3550237
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发表时间：
2001-04
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影响因子：
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通讯作者：
A. Hiratsuka;Kouichi Tobita;H. Saito;Y. Sakamoto;Hiroaki Nakano;K. Ogura;T. Nishiyama;T. Watabe
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作者：
A. Hiratsuka;Kouichi Tobita;H. Saito;Y. Sakamoto;Hiroaki Nakano;K. Ogura;T. Nishiyama;T. Watabe
外消旋体4-羟基-2(E)-壬烯醛（HNE）是一种通过脂质过氧化作用从生物膜释放的活性高毒性产物，在豚鼠肝细胞质中被谷胱甘肽S-转移酶（GSTs）介导的谷胱甘肽偶联解毒(S)优先，醛脱氢酶（ALDH）介导的NAD（+）依赖性氧化(R)优先解毒。gst介导的HNE对映体解毒速率远高于ALDH介导的解毒速率。从豚鼠肝细胞质中分离得到的主要豚鼠gst A1-1、M1-1、M1-2和M1-3*均能催化HNE对映体的(S)优先偶联。在豚鼠的肝脏和其他主要组织中，没有免疫检测到推定的GSTA4-4同源物，该同源物作为一种次要的GST蛋白存在于大鼠、小鼠和人的肝脏中，对HNE具有极高的催化活性。所有肝大鼠gst A1-1(2)、A1-3、A4-4、M1-1、M1-2和M2-2也能催化HNE对映体的(S)优先偶联。
In guinea-pig liver cytosol, racemic 4-hydroxy-2(E)-nonenal (HNE), a reactive and highly toxic product released from biomembranes by lipid peroxidation, was detoxified (S)-preferentially by GSH conjugation mediated by glutathione S-transferases (GSTs) and (R)-preferentially by NAD(+)-dependent oxidation mediated by aldehyde dehydrogenase (ALDH). The GST-mediated detoxification of the HNE enantiomers proceeded at much higher rates than that mediated by ALDH in guinea-pig liver cytosol. All the major guinea-pig GSTs, A1-1, M1-1, M1-2 and M1-3*, isolated from guinea-pig liver cytosol also catalysed the (S)-preferential conjugation of the HNE enantiomers. The liver and other major tissues of guinea-pigs had no immunologically detectable level of a putative GSTA4-4 orthologue, which exists as a minor GST protein in rat, mouse and human livers and exhibits extremely high catalytic activity towards HNE. All the hepatic rat GSTs, A1-1(2), A1-3, A4-4, M1-1, M1-2 and M2-2, also catalysed the (S)-preferential conjugation of HNE enantiomers.