Overexpression of human catalase gene decreases oxidized lipid-induced cytotoxicity in vascular smooth muscle cells.
Overexpression of human catalase gene decreases oxidized lipid-induced cytotoxicity in vascular smooth muscle cells.
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人过氧化氢酶基因的过度表达降低了血管平滑肌细胞中氧化脂质诱导的细胞毒性。
DOI：
10.1161/01.atv.19.8.1912
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Parthasarathy,S
中科院分区：
文献类型：
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作者：
Santanam,N;Aug,N;Zhou,M;Keshava,C;Parthasarathy,S
-过氧化氢(H_2O_2)和氧化脂肪酸等活性氧代谢物是促炎物质，参与包括动脉粥样硬化在内的各种疾病的病理生理过程。这些氧化剂的作用可以通过外加抗氧化剂来抑制，这表明进一步的氧化促进或繁殖。在这项研究中，我们描述了人过氧化氢酶在平滑肌细胞中的稳定过表达，以及这些细胞对过氧化氢和13-羟基过氧十八碳二烯酸(13-HPODE)诱导的细胞毒性的抵抗力。这些结果提出了一种有趣的可能性，即从过氧化的脂肪酸中产生过氧化氢。因此，与13-HPODE和13-羟基十八碳二烯酸共同孵育细胞会导致细胞内过氧化氢的产生。为了解释过氧化氢酶可以克服13-HPODE的影响的观察结果，我们提出了氧化脂肪酸在细胞过氧体中被降解，导致过氧化氢的产生。换句话说，过氧化脂肪酸的细胞效应可以归因于过氧化氢的产生。
—Reactive oxygen metabolites such as hydrogen peroxide (H2O2) and oxidized fatty acids are proinflammatory and are involved in the pathophysiology of various diseases including atherosclerosis. The effects of these oxidants could be inhibited by the external addition of an antioxidant, suggesting the promotion or propagation of further oxidation. In this study, we describe the stable overexpression of human catalase in smooth muscle cells and the resistance of these cells to cytotoxicity induced not only by the addition of H2O2but also by the addition of 13-hydroperoxyoctadecadienoic acid (13-HPODE). The results pose an intriguing possibility of the generation of H2O2from a peroxidized fatty acid. Accordingly, incubation of cells with both 13-HPODE and 13-hydroxyoctadecadienoic acid resulted in the generation of intracellular H2O2. To explain the observed results by which catalase could overcome the effects of 13-HPODE, we propose that oxidized fatty acids are degraded in the cellular peroxisomes, resulting in the generation of H2O2. In other words, the cellular effects of peroxidized fatty acids could be attributed to the generation of H2O2.