Nitric oxide regulates exocytosis by S-nitrosylation of N-ethylmaleimide-sensitive factor.

Abstract	Nitric oxide (NO) inhibits vascular inflammation, but the molecular basis for its anti-inflammatory properties is unknown. We show that NO inhibits exocytosis of Weibel-Palade bodies, endothelial granules that mediate vascular inflammation and thrombosis, by regulating the activity of N-ethylmaleimide-sensitive factor (NSF). NO inhibits NSF disassembly of soluble NSF attachment protein receptor (SNARE) complexes by nitrosylating critical cysteine residues of NSF. NO may regulate exocytosis in a variety of physiological processes, including vascular inflammation, neurotransmission, thrombosis, and cytotoxic T lymphocyte cell killing.
Authors	Kenji Matsushita, Craig N Morrell, Beatrice Cambien, Shui Xiang Yang, Munekazu Yamakuchi, Clare Bao, Makoto R Hara, Richard A Quick, Wangsen Cao, Brian O'Rourke, John M Lowenstein, Jonathan Pevsner, Denisa D Wagner, Charles J Lowenstein
Journal	Cell (Cell) Vol. 115 Issue 2 Pg. 139-50 (Oct 17 2003) ISSN: 0092-8674 [Print] United States
PMID	14567912 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Carrier Proteins Membrane Proteins Recombinant Proteins SNARE Proteins Vascular Endothelial Growth Factor A Vesicular Transport Proteins von Willebrand Factor Nitric Oxide Thrombin N-Ethylmaleimide-Sensitive Proteins Nsf protein, mouse Cysteine NG-Nitroarginine Methyl Ester
Topics	Animals Aorta (cytology) Carrier Proteins (chemistry, genetics, metabolism) Cells, Cultured Cysteine (genetics, metabolism) Endothelium, Vascular (drug effects, metabolism) Exocytosis (drug effects, physiology) Gene Expression Regulation Humans Membrane Proteins (drug effects, metabolism) Mice Mutagenesis, Site-Directed N-Ethylmaleimide-Sensitive Proteins NG-Nitroarginine Methyl Ester (pharmacology) Nitric Oxide (pharmacology) Recombinant Proteins (metabolism) SNARE Proteins Thrombin (pharmacology) Vascular Endothelial Growth Factor A (pharmacology) Vesicular Transport Proteins Weibel-Palade Bodies (drug effects, metabolism) von Willebrand Factor (metabolism)

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