Kim J S, He L, Qian T, Lemasters J J
Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7090, USA.
Curr Mol Med. 2003 Sep;3(6):527-35. doi: 10.2174/1566524033479564.
Reperfusion of ATP-depleted tissues after warm or cold ischemia causes pH-dependent necrotic and apoptotic cell death. In hepatocytes and other cell types as well, the mechanism underlying this reperfusion-induced cell death involves onset of the mitochondrial permeability transition (MPT). Opening of permeability transition (PT) pores in the mitochondrial inner membrane initiates the MPT, an event blocked by cyclosporin A (CsA) and pH less than 7.4. Thus, both acidotic pH and CsA prevent MPT-dependent reperfusion injury. Glycine also blocks reperfusion-induced necrosis but acts downstream of PT pore opening by stabilizing the plasma membrane. After the MPT, ATP availability from glycolysis or other source determines whether cell injury after reperfusion progresses to ATP depletion-dependent necrosis or ATP-requiring apoptosis. Thus, apoptosis and necrosis after reperfusion share a common pathway, the MPT. Cell injury progressing to either necrosis or apoptosis by shared pathways can be more aptly termed necrapoptosis.
温暖或寒冷缺血后ATP耗竭组织的再灌注会导致pH依赖性的坏死和凋亡性细胞死亡。在肝细胞和其他细胞类型中，这种再灌注诱导的细胞死亡的潜在机制涉及线粒体通透性转换（MPT）的发生。线粒体内膜通透性转换（PT）孔的开放引发MPT，这一事件可被环孢素A（CsA）和pH小于7.4所阻断。因此，酸性pH和CsA均可预防MPT依赖性再灌注损伤。甘氨酸也可阻断再灌注诱导的坏死，但通过稳定质膜在PT孔开放的下游起作用。MPT发生后，糖酵解或其他来源的ATP可用性决定了再灌注后的细胞损伤是进展为ATP耗竭依赖性坏死还是ATP依赖性凋亡。因此，再灌注后的凋亡和坏死共享一条共同途径，即MPT。通过共享途径进展为坏死或凋亡的细胞损伤更恰当地称为坏死性凋亡。
