Antioxidant function of the mitochondrial protein SP-22 in the cardiovascular system
Antioxidant function of the mitochondrial protein SP-22 in the cardiovascular system
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DOI：
10.1074/jbc.274.4.2271
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发表时间：
1999-01-22
影响因子：
4.8
通讯作者：
Ikeda, M
中科院分区：
文献类型：
--
作者：
Araki, M;Nanri, H;Ikeda, M
线粒体蛋白SP-22是硫氧还蛋白依赖的过氧化物还原酶家族的成员，提示它可能是线粒体中的抗氧化系统之一，而线粒体是活性氧中间产物产生的主要场所。本研究的目的是检测SP-22是否参与线粒体抗氧化机制以及其表达是否由氧化应激诱导，尤其是线粒体中的那些。当牛主动脉内皮细胞（BAEC）暴露于各种氧化应激（包括线粒体呼吸抑制剂，其增加BAEC线粒体中超氧化物的产生）时，SP-22蛋白的表达增强约1.5-4.6倍。在Fe ~（2+）/二硫苏糖醇或呼吸抑制剂抗霉素A作用后，SP-22 mRNA表达增加2.0-3.5倍，高峰出现在3-6 h。BAEC与SP-22蛋白水平的增加所造成的预处理与轻度氧化应激成为耐受随后的强烈的氧化应激。另一方面，BAEC已耗尽SP-22与反义寡核苷酸对SP-22 mRNA变得更不稳定的氧化应激比对照BAEC。在大鼠心脏心肌梗死实验模型中证实了体内氧化应激对SP-22蛋白的诱导。这些发现表明SP-22在心血管系统的线粒体中起抗氧化剂的作用。
The mitochondrial protein SP-22 has recently been reported to be a member of the thioredoxin-dependent peroxide reductase family, suggesting that it may be one of the antioxidant systems in mitochondria, which are the major site of reactive oxygen intermediate generation, The aim of this study was to examine whether SP-22 is involved in mitochondrial antioxidant mechanisms and whether its expression is induced by oxidative stresses, particularly those in mitochondria. The expression of SP-22 protein was enhanced by about 1.5-4.6-fold when bovine aortic endothelial cells (BAEC) were exposed to various oxidative stresses, including mitochondrial respiratory inhibitors which increased the superoxide generation in BAEC mitochondria. The expression of SP-22 mRNA increased 2.0-3.5-fold with a peak at 3-6 h after exposure to Fe2+/dithiothreitol or a respiratory inhibitor, antimycin A. BAEC with an increased level of SP-22 protein caused by pretreatment with mild oxidative stress became tolerant to subsequent intense oxidative stress. On the other hand, BAEC that had been depleted of SP-22 with an antisense oligodeoxynucleotide against SP-22 mRNA became more labile to oxidative stress than control BAEC. The induction of SP-22 protein by oxidative stress in vivo was demonstrated in an experimental model of myocardial infarction in rat heart. These findings indicate that SP-22 functions as an antioxidant in mitochondria of the cardiovascular system.