Nitric Oxide Attenuates Signal Transduction
| Autor: | Michael S. Goligorsky, Hong Li, Mary Basco, Victor Romanov, Dino A. De Angelis, Sergey Brodsky |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Nitroprusside
Scaffold protein Cholera Toxin Cell signaling Nitric Oxide Synthase Type III Physiology Recombinant Fusion Proteins Vasodilator Agents Caveolin 1 Green Fluorescent Proteins Caveolae Nitric Oxide Caveolins Muscle Smooth Vascular Caveolin Centrifugation Density Gradient Animals Humans Nitric Oxide Donors Enzyme Inhibitors Cells Cultured Endothelin-1 biology Rats Cell biology Nitric oxide synthase Luminescent Proteins Biochemistry biology.protein Calcium Endothelium Vascular Nitric Oxide Synthase Signal transduction Cardiology and Cardiovascular Medicine Ion-Selective Electrodes Signal Transduction |
| Zdroj: | Circulation Research. 88:229-236 |
| ISSN: | 1524-4571 0009-7330 |
| Popis: | Abstract —Caveolae harbor different serpentine receptors, intracellular components of signaling cascades, and certain enzymes, including endothelial nitric oxide synthase (eNOS). The regulation of eNOS activity by Ca 2+ /calmodulin and caveolin has been described. We have previously demonstrated that nitric oxide (NO) can modulate signaling initiated via receptors localized to caveolae. In the present study, we show that NO donors induced an increase in the monomeric form of this scaffolding protein in cultured endothelial cells, the effect mimicked by 8-bromo cGMP. Proximity imaging of endothelial cells transfected with the thermotolerant green fluorescent protein–caveolin-1 construct demonstrated that sodium nitroprusside resulted in the increased fluorescence ratio of 410:470 nm, consistent with the distancing of fluorescently tagged caveolin-1. Pulse labeling of endothelial cells with cholera toxin B subunit indicated that sodium nitroprusside reversibly decreased its binding. Signaling via G protein–coupled receptors resident to caveolae was inhibited by pretreatment with NO donor. The data demonstrate that NO modulation of cell signaling is accomplished in part by regulating the state of caveolin-1 oligomerization. NO-induced attenuation of signaling involves reversible dissociation of caveolin scaffold, thus providing both spatial and temporal modulation of signal transduction. |
| Databáze: | OpenAIRE |
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