Life span and stress resistance of Caenorhabditis elegans are differentially affected by glutathione transferases metabolizing 4-hydroxynon-2-enal
Life span and stress resistance of Caenorhabditis elegans are differentially affected by glutathione transferases metabolizing 4-hydroxynon-2-enal
复制标题
DOI：
10.1016/j.mad.2006.11.025
复制
发表时间：
2007-02-01
影响因子：
5.3
通讯作者：
Zimniak, Piotr
中科院分区：
文献类型：
--
作者：
Ayyadevara, Srinivas;Dandapat, Abhijit;Zimniak, Piotr
脂质过氧化产物4-羟基壬-2-烯醛（4-HNE）作为氧化应激的结果形成，并作为信号分子或在超生理水平上作为毒物。化合物的稳态浓度反映了其生成和代谢之间的平衡，主要通过谷胱甘肽结合。使用基于RNAi的屏幕，我们确定在秀丽隐杆线虫谷胱甘肽转移酶（GST）能够催化4-HNE共轭。RNAi敲低这些GST（GST-5、GST-6、GST-8、GST-10和GST 24基因的产物）使线虫对暴露于4-HNE引起的亲电胁迫敏感。然而，干扰其中两个基因（GST-5和GST-10）的表达会显著缩短生物体的寿命。其他GST的RNAi敲低导致至少同样多的4-HNE加合物，表明对寿命的影响具有组织特异性。我们的研究结果是一致的氧化应激理论的有机体老化，扩大考虑亲电应力作为一个贡献因素。根据这一扩展的假设，脂质过氧化导致在链式反应中形成4-HNE，这放大了原始损伤。4-然后HNE通过形成4-HNE蛋白加合物和蛋白质功能的变化作为“衰老效应物”。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
The lipid peroxidation product 4-hydroxynon-2-enal (4-HNE) forms as a consequence of oxidative stress, and acts as a signaling molecule or, at superphysiological levels, as a toxicant. The steady-state concentration of the compound reflects the balance between its generation and its metabolism, primarily through glutathione conjugation. Using an RNAi-based screen, we identified in Caenorhabditis elegans five glutathione transferases (GSTs) capable of catalyzing 4-HNE conjugation. RNAi knock-down of these GSTs (products of thegst-5, gst-6, gst-8, gst-10, andgst24 genes) sensitized the nematode to electrophilic stress elicited by exposure to 4-HNE. However, interference with the expression of only two of these genes (gst-5 andgst-10) significantly shortened the life span of the organism. RNAi knock-down of the other GSTs resulted in at least as much 4-HNE adducts, suggesting tissue specificity of effects on longevity. Our results are consistent with the oxidative stress theory of organismal aging, broadened by considering electrophilic stress as a contributing factor. According to this extended hypothesis, peroxidation of lipids leads to the formation of 4-HNE in a chain reaction which amplifies the original damage. 4-HNE then acts as an "aging effector" via the formation of 4-HNEprotein adducts, and a resulting change in protein function. (c) 2006 Elsevier Ireland Ltd. All rights reserved.