Molecular mechanisms of ALDH3A1-mediated cellular protection against 4-hydroxy-2-nonenal.
Molecular mechanisms of ALDH3A1-mediated cellular protection against 4-hydroxy-2-nonenal.
复制标题
ALDH3A1介导的细胞保护针对4-羟基-2-非纳尔的分子机制。
DOI：
10.1016/j.freeradbiomed.2012.02.050
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发表时间：
2012-05-01
影响因子：
7.4
通讯作者：
Vasiliou, Vasilis
中科院分区：
文献类型：
--
作者：
Black, William;Chen, Ying;Matsumoto, Akiko;Thompson, David C.;Lassen, Natalie;Pappa, Aglaia;Vasiliou, Vasilis
关键词：
有证据表明，脂质过氧化（LPO）过程中产生的脂质分子的因果关系参与大多数与氧化应激相关的病理生理过程。4-羟基-2-壬烯醛（4-HNE）是LPO衍生的产物，被认为是造成大部分细胞毒性的原因。为了抵消这种醛的不利影响，许多组织已经进化出包括醛脱氢酶（ALDH）的细胞防御机制。我们的实验室先前已经表征了ALDH的组织分布和代谢功能，包括ALDH 3A 1，并证明这些酶可能在保护细胞免受4-HNE侵害方面发挥重要作用。为了进一步表征ALDH 3A 1在氧化应激反应中的作用，稳定转染兔角膜基质细胞系（TRK 43）以过表达人ALDH 3A 1。在用4-HNE处理后研究这些细胞以确定它们以下能力：a）维持细胞活力，B）代谢4-HNE及其谷胱甘肽缀合物，c）防止4-HNE-蛋白质加合物形成，d）防止细胞凋亡，e）维持谷胱甘肽稳态，和f）保护蛋白酶体功能。结果表明ALDH 3A 1对4-HNE具有保护作用。4-HNE加合蛋白的细胞活力测定、形态学评价和蛋白质印迹分析显示，ALDH 3A 1表达保护细胞免受4-HNE的不利影响。基于目前的结果，很明显，ALDH 3A 1提供了特殊的保护，免受病理生理浓度的4-HNE的不利影响，如可能发生在氧化应激期间。
Evidence suggests that aldehydic molecules generated during lipid peroxidation (LPO) are causally involved in most pathophysiological processes associated with oxidative stress. 4-hydroxy-2-nonenal (4-HNE), the LPO-derived product, is believed to be responsible for much of the cytotoxicity. To counteract the adverse effects of this aldehyde, many tissues have evolved cellular defense mechanisms which include the aldehyde dehydrogenases (ALDHs). Our laboratory has previously characterized the tissue distribution and metabolic functions of ALDHs, including ALDH3A1, and demonstrated that these enzymes may play a significant role in protecting cells against 4-HNE. To further characterize the role of ALDH3A1 in the oxidative stress response, rabbit corneal keratocyte cell lines (TRK43) were stably transfected to over-express human ALDH3A1. These cells were studied following treatment with 4-HNE to determine their abilities to: a) maintain cell viability, b) metabolize 4-HNE and its glutathione conjugate, c) prevent 4-HNE-protein adduct formation, d) prevent apoptosis, e) maintain glutathione homeostasis, and f) preserve proteasome function. The results demonstrated a protective role for ALDH3A1 against 4-HNE. Cell viability assays, morphological evaluations and Western blot analyses of 4-HNE-adducted proteins revealed that ALDH3A1 expression protected cells from the adverse effects of 4-HNE. Based on the present results, it is apparent that ALDH3A1 provides exceptional protection from the adverse effects of pathophysiological concentrations of 4-HNE such as may occur during periods of oxidative stress.
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影响因子：
3.3
作者：
Dianzani, MU
通讯作者：
Dianzani, MU
影响因子：
7.4
作者：
Bulteau, AL;Moreau, M;Friguet, B
通讯作者：
Friguet, B
影响因子：
3.4
作者：
ABEDINIA, M;PAIN, T;HOLMES, RS
通讯作者：
HOLMES, RS
影响因子：
4.4
作者：
Choudhary, S;Xiao, TL;Ansari, NH
通讯作者：
Ansari, NH
DOI：
10.1016/0304-4165(85)90137-0
发表时间：
1985-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
LINDAHL, R;BAGGETT, DW;WINTERS, AL
通讯作者：
WINTERS, AL