The nitration of platelet vasodilator stimulated phosphoprotein following exposure to low concentrations of hydrogen peroxide.
Hydrogen peroxide (H2O2) at biologically relevant concentrations acts as a signaling molecule. We have shown previously that H2O2 acts synergistically with nitric oxide (NO) to inhibit platelet aggregation. We found that this synergism may be associated with the increased serine phosphorylation of vasodilator-sensitive phosphoprotein (VASP) by H2O2. In this study we demonstrate that H2O2 in the absence of NO or exogenous haem- containing proteins induces nitration of plateletVASP and other unidentified proteins by a mechanism that may involve the formation of peroxynitrite. The nitration was NO-dependent, but independent of oxidative stress and guanylyl cyclcase. The flavanoid epigallocatechin gallate (ECGC) completely suppressed nitration and was also shown to inhibit partially platelet activation by other agonists. Importantly, protein nitration was reversible, or at least the nitrated tyrosine residues are converted to a form not recognized by anti-nitrotyrosine antibodies. The loss of nitrated VASP was still evident in the presence of membrane permeable protease inhibitors. In conclusion, as H2O2 can inhibit platelet function, the nitration of VASP, a protein critical for actin cytoskeletal rearrangement, may represent a novel mechanism important in the regulation of platelets shape change leading to inhibition of platelets aggregation and the formation of blood clot.
Hampstead Campus University College London, London NW32PF, UK.
Mojhgan
M
Sabetkar
Sylvia Y
SY
Low
Nickolas J
NJ
Bradley
Michael
M
Jacobs
Khalid M
KM
Naseem
K
K
Richard Bruckdorfer
D001792:Blood Platelets / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism* / Q000502:physiology; D009566:Nitrates; D009569:Nitric Oxide / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism* / Q000502:physiology; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors; D011499:Protein Processing, Post-Translational; D000098662:Vasodilator-Stimulated Phosphoprotein
D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D009566:Nitrates; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D000098662:Vasodilator-Stimulated Phosphoprotein; D009569:Nitric Oxide; D002392:Catechin; D006861:Hydrogen Peroxide; C045651:epigallocatechin gallate