Pavón Natalia, Correa Francisco, Buelna-Chontal Mabel, Hernández-Esquivel Luz, Chávez Edmundo
Departamento de Farmacología, Instituto Nacional de Cardiología, Ignacio Chávez, México D. F. 014080, México.
Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología, Ignacio Chávez, Mexico.
Life Sci. 2015 Oct 15;139:108-13. doi: 10.1016/j.lfs.2015.08.011. Epub 2015 Aug 24.
Mitochondrial permeability transition is a process established through massive Ca(2+) load in addition to an inducer reagent. Ebselen (Ebs), an antioxidant seleno compound, has been introduced as a reagent which inhibits mitochondrial dysfunction induced by permeability transition. Paradoxically enough, it has been shown that Ebs may also be able to induce the opening of the mitochondrial non-selective pores. This study was performed with the purpose of establishing the membrane system involved in Ebs-induced pore opening.
Permeability transition was appraised by analyzing the following: i) matrix Ca(2+) release, and mitochondrial swelling, ii) efflux of cytochrome c, and iii) the inhibition of superoxide dismutase. All of these adverse reactions were inhibited by N-ethylmaleimide and cyclosporin A.
At concentrations from 5 to 20 μM, we found that Ebs induces non-specific membrane permeability. Remarkably, Ebs blocks the binding of the fluorescent reagent eosin-5-maleimide to the thiol groups of the adenine nucleotide translocase.
Based on the above, it is tempting to hypothesize that Ebs induces pore opening through its binding to the ADP/ATP carrier.
线粒体通透性转变是一个除诱导剂外还通过大量钙离子负荷建立的过程。依布硒啉（Ebs）是一种抗氧化硒化合物，已被引入作为一种抑制通透性转变诱导的线粒体功能障碍的试剂。然而，奇怪的是，已表明Ebs也可能能够诱导线粒体非选择性孔的开放。本研究旨在确定参与Ebs诱导的孔开放的膜系统。
通过分析以下内容评估通透性转变：i）基质钙离子释放和线粒体肿胀，ii）细胞色素c外流，以及iii）超氧化物歧化酶的抑制。所有这些不良反应均被N-乙基马来酰亚胺和环孢菌素A抑制。
在5至20μM的浓度下，我们发现Ebs诱导非特异性膜通透性。值得注意的是，Ebs阻断荧光试剂曙红-5-马来酰亚胺与腺嘌呤核苷酸转位酶硫醇基团的结合。
基于上述情况，很容易假设Ebs通过其与ADP/ATP载体的结合诱导线粒体孔开放。
