Tyurina Y Y, Shvedova A A, Kawai K, Tyurin V A, Kommineni C, Quinn P J, Schor N F, Fabisiak J P, Kagan V E
Department of Environmental and Occupational Health, University of Pittsburgh, 260 Kappa Drive, RIDC Park, Pittsburgh, PA 15238, USA.
Toxicology. 2000 Aug 7;148(2-3):93-101. doi: 10.1016/s0300-483x(00)00199-2.
The role of phospholipids in apoptosis signaling and the relationship between oxidation of phosphatidylserine and its redistribution in the plasma membrane were studied. A novel method for detection of site-specific phospholipid peroxidation based on the use of cis-parinaric acid as a reporter molecule metabolically integrated into membrane phospholipids in living cells was employed. When several tissue culture cell lines and different exogenous oxidants were used, the relationship between the oxidation of phosphatidylserine and apoptosis has been revealed. The plasma membrane was the preferred site of phosphatidylserine oxidation in cells. It was shown that selective oxidation of phosphatidylserine precedes its translocation from the inside to the outside surface of the plasma membrane during apoptosis. A model is proposed in which cytochrome c released from mitochondria by oxidative stress binds to phosphatidylserine located at the cytoplasmic surface of the plasma membrane and induces its oxidation. Interaction of peroxidized phosphatidylserine with aminophospholipid translocase causes inhibition of the enzyme relevant to phosphatidylserine externalization.
研究了磷脂在细胞凋亡信号传导中的作用以及磷脂酰丝氨酸氧化与其在质膜中重新分布之间的关系。采用了一种基于使用顺式-杷荏酸作为报告分子代谢整合到活细胞的膜磷脂中的检测位点特异性磷脂过氧化的新方法。当使用几种组织培养细胞系和不同的外源性氧化剂时，揭示了磷脂酰丝氨酸氧化与细胞凋亡之间的关系。质膜是细胞中磷脂酰丝氨酸氧化的首选位点。结果表明，在细胞凋亡过程中，磷脂酰丝氨酸的选择性氧化先于其从质膜内表面向外表面的易位。提出了一个模型，其中通过氧化应激从线粒体释放的细胞色素c与位于质膜细胞质表面的磷脂酰丝氨酸结合并诱导其氧化。过氧化的磷脂酰丝氨酸与氨基磷脂转位酶的相互作用导致与磷脂酰丝氨酸外化相关的酶受到抑制。
