Role for uncoupling protein-2 as a regulator of mitochondrial hydrogen peroxide generation
Role for uncoupling protein-2 as a regulator of mitochondrial hydrogen peroxide generation
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DOI：
10.1096/fasebj.11.10.9271366
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发表时间：
1997-08-01
期刊：
影响因子：
4.8
通讯作者：
Casteilla, L
中科院分区：
文献类型：
--
作者：
NegreSalvayre, A;Hirtz, C;Casteilla, L
根据线粒体呼吸的状态，呼吸链产生超氧阴离子转化为过氧化氢。两个解偶联蛋白（UCP）能够调节呼吸链和ATP合成之间的耦合，现在被确定，并可能参与线粒体过氧化氢的产生。UCP 1对棕色脂肪组织（BAT）具有特异性，而UCP 2在许多组织中表达，特别是在单核细胞/巨噬细胞中。BAT的线粒体组分与GDP，UCP 1的抑制剂，预孵育诱导线粒体膜电位上升（罗丹明123摄取评估）和H2 O2的生产。解偶联剂逆转了这种效应。肝线粒体表现出类似的表型。CDP也能够提高膜电位和H2 O2生产的非实质细胞表达UCP 2的线粒体，但完全无效的线粒体从肝细胞剥夺UCP 2。GDP效应也观察到与脾脏或胸腺的线粒体部分，其中高度表达UCP 2。总之，这些结果强烈表明，UCP 2是敏感的GDP和UCPs，特别是UCP 2，能够调节H2 O2线粒体的产生。这支持了UCP 2在涉及线粒体产生的自由基的细胞（病理）生理过程中的作用，如氧化损伤、炎症或凋亡。
According to the state of mitochondrial respiration, the respiratory chain generates superoxide anions converted into hydrogen peroxide. Two uncoupling proteins (UCP) able to modulate the coupling between the respiratory chain and ATP synthesis are now identified and could be involved in mitochondrial H2O2 generation. UCP1 is specific to brown adipose tissue (BAT) whereas UCP2 is expressed in numerous tissues, particularly in monocytes/macrophages. Preincubation of BAT mitochondrial fractions with GDP, an inhibitor of UCP1, induced a rise in mitochondrial membrane potential (assessed by rhodamine 123 uptake) and H2O2 production. An uncoupling agent reversed this effect. Liver mitochondria exhibited a similar phenotype. CDP was also able to raise membrane potential and H2O2 production of the mitochondria from nonparenchymal cells expressing UCP2, but was completely ineffective on mitochondria from hepatocytes deprived of UCP2. The GDP effect was also observed with mitochondrial fractions of the spleen or thymus, which highly expressed UCP2. Altogether, these results strongly suggest that UCP2 is sensitive to GDP and that the UCPs, particularly UCP2, are able to modulate H2O2 mitochondrial generation. This supports a role for UCP2 in cellular (patho-) physiological processes involving free radicals generated by mitochondria, such as oxidative damage, inflammation, or apoptosis.