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.

Nitric oxide inhibits insulin-degrading enzyme activity and function through S-nitrosylation

“…The concentrations of the artificial NO donors used in this study may seem superphysiologic; however, the amount of NO released from these compounds is actually at least 100-fold less than the concentration of compound used. This brings the amount of NO in these assays into the micromolar and sub-micromolar range, well within the range of NO known to be released by iNOS intracellularly [47,48]. Therefore, S-nitrosylation of IDE is a potentially physiologically relevant mechanism of metabolic control for the actions of IDE.…”

Cholesterol transport from late endosomes to the Golgi regulates t-SNARE trafficking, assembly, and function

“…SNAP23 and syntaxin-4 interacting with VAMP3 (cellubrevin) in endothelial cells has been described (Matsushita et al , 2003; Pulido et al , 2010). Therefore we also examined the capacity of VAMP3 to form ternary complexes with SNAP23 and syntaxin-4 in CHOwt and CHO-A6 cells.…”

Redox-based regulation of signal transduction: Principles, pitfalls, and promises

“…Overall, the technique has been a major advance, not only opening the field to outside disciplines but also serving to to verify earlier work through the 1990's using more cumbersome techniques (mercurycoupled photolysis chemiluminescence and various other chemical and spectroscopic methods). Today, anti SNO-antibodies are also commercially available and have been used both in various histological analysis, Westerns, and immunoprecipitations [14,225,226]. Similar approaches have been taken towards the identification of S-glutathionylated proteins.…”