LOSS OF MEMBRANE PHOSPHOLIPID ASYMMETRY IN PLATELETS AND RED-CELLS MAY BE ASSOCIATED WITH CALCIUM-INDUCED SHEDDING OF PLASMA-MEMBRANE AND INHIBITION OF AMINOPHOSPHOLIPID TRANSLOCASE
LOSS OF MEMBRANE PHOSPHOLIPID ASYMMETRY IN PLATELETS AND RED-CELLS MAY BE ASSOCIATED WITH CALCIUM-INDUCED SHEDDING OF PLASMA-MEMBRANE AND INHIBITION OF AMINOPHOSPHOLIPID TRANSLOCASE
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DOI：
10.1016/0005-2736(90)90058-v
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发表时间：
1990-07-24
期刊：
影响因子：
--
通讯作者：
ZWAAL, RFA
中科院分区：
文献类型：
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作者：
COMFURIUS, P;SENDEN, JMG;ZWAAL, RFA
血小板和红细胞中钙的内流产生从质膜脱落的囊泡的形成。当在凝血酶原酶测定中用作磷脂源时，脱落的时间过程与两种细胞刺激凝血酶原酶活性的能力密切相关。这反映了磷脂酰丝氨酸的表面暴露增加，推测是由于膜不对称性的损失。有证据表明，脱落囊泡有一个随机的磷脂分布，而残留的细胞表现出渐进的损失膜磷脂不对称时，更多的脱落发生。细胞内钙的去除产生的残余细胞的促凝活性的降低，但不是脱落的囊泡。这与氨基磷脂移位酶活性的再活化一致，首先被细胞内钙抑制，随后在钙去除后再活化。氨基磷脂移位酶的参与进一步得到以下观察结果的支持：促凝血活性的可逆性也依赖于代谢ATP和还原巯基。这一可逆性过程在脱落囊泡中不明显的发现可能归因于不存在移位酶或缺乏ATP。这些数据支持并扩展了西姆斯等人（（1989）J. Biol. Chem. 264，17049-17057）提出的建议，即发生脱落所需的膜融合产生膜磷脂的瞬时翻转位点。 此外，目前的结果表明，混乱的膜磷脂只能发生氨基磷脂移位酶是无活性的。
Influx of calcium in platelets and red cells produces formation of vesicles shed from the plasma membrane. The time course of the shedding closely correlates with the ability of both cells to stimulate prothrombinase activity when used as a source of phospholipid in the prothrombinase assay. This reflects increased surface exposure of phosphatidylserine, presumably resulting from a loss in membrane asymmetry. Evidence is presented that the shed vesicles have a random phospholipid distribution, while the remnant cells show a progressive loss of membrane phospholipid asymmetry when more shedding occurs. Removal of intracellular calcium produces a decrease of procoagulant activity of the remnant cells but not of that of the shed vesicles. This is consistent with reactivation of aminophospholipid translocase activity, being first inhibited by intracellular calcium and subsequently reactivated upon calcium removal. Involvement of aminophospholipid translocase is further supported by the observation that reversibility of procoagulant activity is also dependent on metabolic ATP and reduced sulfhydryl groups. The finding that this reversibility process is not apparent in shed vesicles may be ascribed to the absence of translocase or to a lack of ATP. These data support and extend the suggestion made by Sims et al. ((1989) J. Biol. Chem. 264, 17049-17057) that membrane fusion, which is required for shedding to occur, produces transient flip-flop sites for membrane phospholipids. Furthermore, the present results indicate that scrambling of membrane phospholipids can only occur provided that aminophospholipid translocase is inactive.