Ethanol stimulates shape change in human platelets by activation of phosphoinositide-specific phospholipase C.

Ethanol stimulates shape change in human platelets by activation of phosphoinositide-specific phospholipase C.
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乙醇通过激活磷酸肌醇特异性磷脂酶 C 来刺激人血小板的形状变化。

DOI:
10.1016/0003-9861(88)90472-9
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发表时间:
1988
影响因子:
3.9
通讯作者:
Hoek,JB
Hoek,JB
中科院分区:
生物学3区
文献类型:
--
作者:
Rubin,R;Ponnappa,BC;Thomas,AP;Hoek,JB

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乙醇对人血小板的给药导致快速的形状变化,在30 s内最大。乙醇在任何时候都不引起ATP的聚集或分泌,并抑制胶原诱导的聚集。在血小板内钙指示剂fura 2加载,乙醇诱导钙从内部,凝血酶敏感池的快速动员。胞浆钙在5秒内增加到最大值,并在随后的5分钟内缓慢下降到接近基础水平。乙醇对钙的动员与磷脂酸的快速形成和4,5-二磷酸磷脂酰肌醇水平的降低相一致,如在32 P标记的血小板中所测量的。在用肌-[2- 3 H]肌醇标记的血小板中,乙醇在10秒内引起(1,4,5)-三磷酸肌醇和二磷酸肌醇水平增加20-30%。乙醇还诱导肌球蛋白轻链(20 kDa)和40 kDa蛋白(蛋白激酶C的已知底物)的瞬时磷酸化。结果表明,乙醇激活人血小板中的磷酸肌醇特异性磷脂酶C。随后的细胞内钙的动员和蛋白激酶C的激活可以解释乙醇诱导的形状变化。
Administration of ethanol to human platelets resulted in a rapid shape change which was maximal within 30 s. Ethanol did not cause aggregation or secretion of ATP at any time and inhibited aggregation induced by collagen. In platelets that were loaded with the intracellular calcium indicator fura2, ethanol induced a rapid mobilization of calcium from internal, thrombin-sensitive pools. Cytosolic calcium increased to a maximum within 5 s and decreased slowly over the ensuing 5 min to near basal levels. The mobilization of calcium by ethanol coincided with the rapid formation of phosphatidic acid and a decrease in the level of phosphatidylinositol 4,5-bisphosphate, as measured in32P-labeled platelets. In platelets labeled withmyo-[2-3H]inositol, ethanol caused a 20–30% increase in the levels of inositol (1,4,5)-trisphosphate and inositol bisphosphate within 10 s. Ethanol also induced the transient phosphorylation of myosin light chain (20 kDa) and a 40 kDa protein, a known substrate for protein kinase C. The results indicate that ethanol activates phosphoinositide-specific phospholipase C in human platelets. The subsequent mobilization of intracellular calcium and activation of protein kinase C can account for the shape change induced by ethanol.
离子载体 A23187 对人血小板磷脂酶 C 的激活完全依赖于环加氧酶产物和 ADP。
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