Decreased complex II respiration and HNE-modified SDH subunit in diabetic heart
Decreased complex II respiration and HNE-modified SDH subunit in diabetic heart
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DOI：
10.1016/j.freeradbiomed.2005.10.040
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发表时间：
2006-03-01
影响因子：
7.4
通讯作者：
Romani, AMP
中科院分区：
文献类型：
--
作者：
Lashin, OM;Szweda, PA;Romani, AMP
一些研究表明，线粒体在糖尿病心肌病的发病机制中发挥作用，尽管所涉及的机制仍有争议。在本研究中，我们报告说，状态3的耗氧量减少了类似于35%，谷氨酸和类似于30%，琥珀酸在线粒体糖尿病大鼠心脏相比，控制。在这些线粒体中，复合物1和复合物If的酶活性也降低到可比较的程度。使用抗体识别脂质过氧化产物4-羟基壬烯醛修饰的蛋白质的线粒体蛋白质模式的Western印迹分析表明，琥珀酸脱氢酶的含EAD亚基是这种高反应性醛的靶点之一。在糖尿病6周或12周的大鼠中，补充胰岛素2周可降低4-羟基壬烯醛修饰的蛋白质水平，并将线粒体呼吸和酶活性恢复至对照水平。综合起来，这些结果：（1）表明4-羟基壬烯醛在糖尿病线粒体内内源性产生并与选择性线粒体蛋白形成加合物，（2）鉴定这些蛋白之一为琥珀酸脱氢酶的亚基，和（3）提供胰岛素治疗可逆转和改善糖尿病条件下的自由基损伤和线粒体功能的有力证据。(c)2005年爱思唯尔公司All rights reserved.
Several lines of research suggest that mitochondria play a role in the etiopathogenesis of diabetic cardiomyopathy, although the mechanisms involved are still debated. In the present study, we report that State 3 oxygen consumption decreases by similar to 35% with glutamate and by similar to 30% with succinate in mitochondria from diabetic rat hearts compared to controls. In these mitochondria the enzymatic activities of complex 1 and complex If are also decreased to a comparable extent. Western blot analysis of mitochondrial protein pattern using antibodies recognizing proteins modified by the lipid peroxidation product 4-hydroxynonenal indicates the EAD-containing subunit of succinate dehydrogenase as one of the targets of this highly reactive aldehyde. In rats diabetic for 6 or 12 weeks, insulin supplementation for 2 weeks decreases the level of protein modified by 4-hydroxynonenal and restores mitochondrial respiration and enzyme activity to control level. Taken together, these results: (1) indicate that 4-hydroxynonenal is endogenously produced within diabetic mitochondria and forms an adduct with selective mitochondrial proteins, (2) identify one of these proteins as a subunit of succinate dehydrogenase, and (3) provide strong evidence that insulin treatment can reverse and ameliorate free radical damage and mitochondrial function under diabetic conditions. (c) 2005 Elsevier Inc. All rights reserved.