Regulation of platelet granule exocytosis by S-nitrosylation

被引:112
作者
Morrell, CN
Matsushita, K
Chiles, K
Scharpf, RB
Yamakuchi, M
Mason, RJA
Bergmeier, W
Mankowski, JL
Baldwin, WM
Faraday, N
Lowenstein, CJ
机构
[1] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Dept Comparat Med, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA
[4] Johns Hopkins Univ, Sch Med, Dept Anesthesiol, Baltimore, MD 21205 USA
[5] Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA
[6] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA
关键词
alpha-granules; nitric oxide;
D O I
10.1073/pnas.0408310102
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 a-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.
引用
收藏
页码:3782 / 3787
页数:6
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