Kagan V E, Fabisiak J P, Shvedova A A, Tyurina Y Y, Tyurin V A, Schor N F, Kawai K
Department of Environmental and Occupational Health, University of Pittsburgh, 260 Kappa Drive, Pittsburgh, PA 15238, USA.
FEBS Lett. 2000 Jul 14;477(1-2):1-7. doi: 10.1016/s0014-5793(00)01707-5.
Active maintenance of membrane phospholipid asymmetry is universal in normal cell membranes and its disruption with subsequent externalization of phosphatidylserine is a hallmark of apoptosis. Externalized phosphatidylserine appears to serve as an important signal for targeting recognition and elimination of apoptotic cells by macrophages, however, the molecular mechanisms responsible for phosphatidylserine translocation during apoptosis remain unresolved. Studies have focused on the function of aminophospholipid translocase and phospholipid scramblase as mediators of this process. Here we present evidence that unique oxidative events, represented by selective oxidation of phosphatidylserine, occur during apoptosis that could promote phosphatidylserine externalization. We speculate that selective phosphatidylserine oxidation could affect phosphatidylserine recognition by aminophospholipid translocase and/or directly result in enzyme inhibition. The potential interactions between the anionic phospholipid phosphatidylserine and the redox-active cationic protein effector of apoptosis, cytochrome c, are presented as a potential mechanism to account for selective oxidation of phosphatidylserine during apoptosis. Thus, cytochrome c-mediated phosphatidylserine oxidation may represent an important component of the apoptotic pathway.
膜磷脂不对称性的主动维持在正常细胞膜中普遍存在，而其破坏以及随后磷脂酰丝氨酸的外化是细胞凋亡的一个标志。外化的磷脂酰丝氨酸似乎是巨噬细胞靶向识别和清除凋亡细胞的重要信号，然而，凋亡过程中磷脂酰丝氨酸易位的分子机制仍未解决。研究集中在氨基磷脂转位酶和磷脂 scramblase 作为这一过程的介质的功能上。在这里，我们提供证据表明，在凋亡过程中发生了以磷脂酰丝氨酸选择性氧化为代表的独特氧化事件，这可能促进磷脂酰丝氨酸的外化。我们推测，选择性磷脂酰丝氨酸氧化可能影响氨基磷脂转位酶对磷脂酰丝氨酸的识别和/或直接导致酶抑制。阴离子磷脂磷脂酰丝氨酸与凋亡的氧化还原活性阳离子蛋白效应物细胞色素 c 之间的潜在相互作用被提出，作为解释凋亡过程中磷脂酰丝氨酸选择性氧化的潜在机制。因此，细胞色素 c 介导的磷脂酰丝氨酸氧化可能代表凋亡途径的一个重要组成部分。
