Morrell Craig N, Matsushita Kenji, Chiles Kelly, Scharpf Robert B, Yamakuchi Munekazu, Mason Rebecca J A, Bergmeier Wolfgang, Mankowski Joseph L, Baldwin William M, Faraday Nauder, Lowenstein Charles J
Department of Comparative Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Proc Natl Acad Sci U S A. 2005 Mar 8;102(10):3782-7. doi: 10.1073/pnas.0408310102. Epub 2005 Feb 28.
Nitric oxide (NO) regulates platelet activation by cGMP-dependent mechanisms and by mechanisms that are not completely defined. Platelet activation includes exocytosis of platelet granules, releasing mediators that regulate interactions between platelets, leukocytes, and endothelial cells. Exocytosis is mediated in part by N-ethylmaleimide-sensitive factor (NSF), an ATPase that disassembles complexes of soluble NSF attachment protein receptors. We now demonstrate that NO inhibits exocytosis of dense granules, lysosomal granules, and alpha-granules from human platelets by S-nitrosylation of NSF. Platelets lacking endothelial NO synthase show increased rolling on venules, increased thrombosis in arterioles, and increased exocytosis in vivo. Regulation of exocytosis is thus a mechanism by which NO regulates thrombosis.
一氧化氮（NO）通过依赖环磷酸鸟苷（cGMP）的机制以及尚未完全明确的机制来调节血小板活化。血小板活化包括血小板颗粒的胞吐作用，释放调节血小板、白细胞和内皮细胞之间相互作用的介质。胞吐作用部分由N - 乙基马来酰亚胺敏感因子（NSF）介导，NSF是一种ATP酶，可拆解可溶性NSF附着蛋白受体复合物。我们现在证明，NO通过对NSF进行S - 亚硝基化来抑制人血小板致密颗粒、溶酶体颗粒和α颗粒的胞吐作用。缺乏内皮型NO合酶的血小板在小静脉上的滚动增加，在小动脉中的血栓形成增加，并且在体内的胞吐作用增强。因此，胞吐作用的调节是NO调节血栓形成的一种机制。
