缺血期间电子传递的阻断可保护 bcl-2 并抑制线粒体通透性转换孔的开放。
Blockade of electron transport during ischemia preserves bcl-2 and inhibits opening of the mitochondrial permeability transition pore.
机构信息
Department of Medicine (Division of Cardiology), Virginia Commonwealth University, Richmond, VA 23298, USA.
出版信息
FEBS Lett. 2011 Mar 23;585(6):921-6. doi: 10.1016/j.febslet.2011.02.029. Epub 2011 Feb 25.
Abstract
Myocardial ischemia damages the electron transport chain and augments cardiomyocyte death during reperfusion. To understand the relationship between ischemic mitochondrial damage and mitochondrial-driven cell death, the isolated perfused heart underwent global stop-flow ischemia with and without mitochondrial protection by reversible blockade of electron transport. Ischemic damage to electron transport depleted bcl-2 content and favored mitochondrial permeability transition (MPT). Reversible blockade of electron transport preserved bcl-2 content and attenuated calcium-stimulated mitochondrial swelling. Thus, the damaged electron transport chain leads to bcl-2 depletion and MPT opening. Chemical inhibition of bcl-2 with HA14-1 also dramatically increased mitochondrial swelling, augmented by exogenous H(2)O(2) stress, indicating that bcl-2 depleted mitochondria are poised to undergo MPT during the enhanced oxidative stress of reperfusion.
摘要
心肌缺血在再灌注期间损伤电子传递链并增强心肌细胞死亡。为了了解缺血性线粒体损伤与线粒体驱动的细胞死亡之间的关系，进行了分离的灌注心脏的全停流缺血，并用电子传递的可逆阻断进行了线粒体保护。电子传递的缺血性损伤耗尽了 bcl-2 含量，并有利于线粒体通透性转换（MPT）。电子传递的可逆阻断保存了 bcl-2 含量并减弱了钙刺激的线粒体肿胀。因此，受损的电子传递链导致 bcl-2 耗竭和 MPT 开放。用 HA14-1 进行 bcl-2 的化学抑制也显著增加了线粒体肿胀，并且外源性 H2O2 应激进一步增强，表明在再灌注期间增强的氧化应激下，bcl-2 耗竭的线粒体准备进行 MPT。
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