Leoncini G, Signorello M G
Istituto di Chimica Biologica, Università di Genova, Genoa, Italy.
Biochem Pharmacol. 1999 Oct 15;58(8):1293-9. doi: 10.1016/s0006-2952(99)00205-1.
The data presented in this report show that N-ethylmaleimide (NEM) is a powerful inhibitor of thrombin-induced platelet aggregation. NEM increased guanosine 3', 5'-cyclic monophosphate (cGMP) and adenosine 3', 5'-cyclic monophosphate (cAMP) levels in intact cells. The inhibition of cAMP high-affinity phosphodiesterase and cGMP phosphodiesterase was implicated in the elevation of the cyclic nucleotides. NEM dose dependently blocked the thrombin-stimulated, but not the phorbol myristate acetate-dependent phosphorylation of the protein kinase C substrate pleckstrin. Myosin light chain phosphorylation was also inhibited by NEM. In addition, the sulphydryl reagent inhibited Ca2+ mobilisation induced by thrombin. The data indicate that phospholipase C activation by thrombin is interrupted by NEM at the level of receptor-mediated signal transduction.
本报告中呈现的数据表明，N-乙基马来酰亚胺（NEM）是凝血酶诱导的血小板聚集的强效抑制剂。NEM可提高完整细胞中鸟苷3'，5'-环磷酸（cGMP）和腺苷3'，5'-环磷酸（cAMP）的水平。环核苷酸水平的升高与cAMP高亲和力磷酸二酯酶和cGMP磷酸二酯酶的抑制有关。NEM剂量依赖性地阻断凝血酶刺激的蛋白激酶C底物普列克底物蛋白的磷酸化，但不阻断佛波酯肉豆蔻酸酯乙酸盐依赖性的磷酸化。肌球蛋白轻链磷酸化也受到NEM的抑制。此外，这种巯基试剂抑制凝血酶诱导的Ca2+动员。数据表明，在受体介导的信号转导水平上，NEM会中断凝血酶对磷脂酶C的激活。
