Shear stress increases the amount of S-nitrosylated molecules in endothelial cells: important role for signal transduction.
Laminar flow (shear stress) is an important stimulus for nitric oxide (NO) synthesis in endothelial cells. NO can react with free SH-groups of different proteins leading to S-nitrosylation. Since S-nitrosylation of proteins is an important regulator of protein functions, we investigated the effect of endogenously synthesized NO. Exposure to shear stress significantly increased the overall S-nitrosylation of proteins in endothelial cells. Interestingly, shear stress increased S-nitrosylation of specific target proteins, i.e. the catalytic p17 subunit of caspase-3, the GTPase p21ras and the oxidoreductase thioredoxin. S-nitrosylation resulted in an inhibition of caspase-3 and in an augmented activity of p21ras and thioredoxin. These data suggest that long term exposure to shear stress exerts its different atheroprotective effects at least in part via increased S-nitrosylation of specific signaling proteins.
Hoffmann
Jörg
J
Department of Internal Medicine IV, University of Frankfurt, Theodor-Stern-Kai 7, Frankfurt, Germany.
Dimmeler
Stefanie
S
Haendeler
Judith
J
D053148:Caspase 3; D020169:Caspases / Q000737:chemistry; D002478:Cells, Cultured; D003545:Cysteine / Q000031:analogs & derivatives* / Q000032:analysis*; D004730:Endothelium, Vascular / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D016283:Proto-Oncogene Proteins p21(ras) / Q000737:chemistry / Q000378:metabolism; D026403:S-Nitrosothiols / Q000032:analysis*; D015398:Signal Transduction; D013314:Stress, Mechanical; D013879:Thioredoxins / Q000737:chemistry / Q000378:metabolism
D026403:S-Nitrosothiols; D013879:Thioredoxins; C021315:S-nitrosocysteine; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D003545:Cysteine