Regulation of platelet granule exocytosis by S-nitrosylation

Craig N. Morrell, Kenji Matsushita, Kelly Chiles, Robert B. Scharpf, Munekazu Yamakuchi, Rebecca J.A. Mason, Wolfgang Bergmeier, Joseph L. Mankowski, William M. Baldwin, Nauder Faraday, Charles J. Lowenstein

Research output: Contribution to journalArticle

Abstract

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 α-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.

Original languageEnglish (US)
Pages (from-to)3782-3787
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number10
DOIs
StatePublished - Mar 8 2005

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Keywords

  • Nitric oxide
  • α-granules

ASJC Scopus subject areas

  • General

Cite this

Morrell, C. N., Matsushita, K., Chiles, K., Scharpf, R. B., Yamakuchi, M., Mason, R. J. A., Bergmeier, W., Mankowski, J. L., Baldwin, W. M., Faraday, N., & Lowenstein, C. J. (2005). Regulation of platelet granule exocytosis by S-nitrosylation. Proceedings of the National Academy of Sciences of the United States of America, 102(10), 3782-3787. https://doi.org/10.1073/pnas.0408310102