García Noemí, Correa Francisco, Chávez Edmundo
Departamento de Bioquímica, Instituto Nacional de Cardiología, Ignacio Chávez, México, D.F., México 014080.
J Bioenerg Biomembr. 2005 Feb;37(1):17-23. doi: 10.1007/s10863-005-4119-9.
In this work we studied permeability transition by incubating mitochondria in the presence of 50 muM Ca(2+) and malate/glutamate as substrates. This condition, besides inducing the release of pyridine nucleotides, promotes the generation of reactive oxygen-derived species by the complex I of the respiratory chain. The latter leads to the opening of the mitochondrial permeability transition pore. Ca(2+) release, mitochondrial swelling and collapse of the transmembrane electric potential, were analyzed to assess this process. We propose that the mechanism for pore opening, in addition to the oxidative stress, involves the uncoupling effect of fatty acids providing activation of phospholipase A2, lipid peroxidation, and the oxidation of membrane thiols. This proposal emerges from the data indicating the protective effect of bovine serum albumin and N-ethylmaleimide. The key role of reactive oxygen species was implied based on the fact that the scavenger alpha-phenyl-tert-butyl nitrone inhibited pore opening.
在这项工作中，我们通过在50μM Ca(2+)以及苹果酸/谷氨酸作为底物存在的情况下孵育线粒体来研究通透性转变。这种条件除了诱导吡啶核苷酸的释放外，还通过呼吸链复合体I促进活性氧衍生物种的生成。后者导致线粒体通透性转变孔的开放。分析Ca(2+)释放、线粒体肿胀和跨膜电势的崩溃以评估此过程。我们提出，除氧化应激外，孔开放的机制还涉及脂肪酸的解偶联作用，从而激活磷脂酶A2、脂质过氧化以及膜硫醇的氧化。这一观点源于表明牛血清白蛋白和N-乙基马来酰亚胺具有保护作用的数据。基于清除剂α-苯基-叔丁基硝酮抑制孔开放这一事实，暗示了活性氧物种的关键作用。
