title: N-ethylmaleimide-sensitive factor: a redox sensor in exocytosis.
abstract: Vascular injury triggers endothelial exocytosis of granules, releasing pro-inflammatory and pro-thrombotic mediators into the blood. Nitric oxide (NO) and reactive oxygen species (ROS) limit vascular inflammation and thrombosis by inhibiting endothelial exocytosis. NO decreases exocytosis by regulating the activity of the N-ethylmaleimide-sensitive factor (NSF), a central component of the exocytic machinery. NO nitrosylates specific cysteine residues of NSF, thereby inhibiting NSF disassembly of the soluble NSF attachment protein receptor (SNARE). NO also modulates exocytosis of other cells; for example, NO regulates platelet activation by inhibiting alpha-granule secretion from platelets. Other radicals besides NO can regulate exocytosis as well. For example, H(2)O(2) inhibits exocytosis by oxidizing NSF. Using site-directed mutagenesis, we have defined the critical cysteine residues of NSF, and found that one particular cysteine residue, C264, renders NSF sensitive to oxidative stress. Since radicals such as NO and H(2)O(2) inhibit NSF and decrease exocytosis, NSF may act as a redox sensor, modulating exocytosis in response to changes in oxidative stress.
authors.affiliation: Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. clowenst@jhmi.edu
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Lowenstein
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Tsuda
mesh_terms: D000818:Animals; D002465:Cell Movement; D005089:Exocytosis; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism; D052066:N-Ethylmaleimide-Sensitive Proteins / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D010084:Oxidation-Reduction
chemical_list: D009569:Nitric Oxide; D052066:N-Ethylmaleimide-Sensitive Proteins