The role of protein nitration in the inhibition of platelet activation by peroxynitrite

FEBS Letters

Bruckdorfer, K.Richard¹  Naseem, Khalid M²  Sabetkar, Mojhgan¹  Low, Sylvia Y¹ 

[1]Departments of Biochemistry and Molecular Biology, Royal Free and University College Medical School (University College London), Rowland Hill Street, London NW3 2PF, UK

[2]Department of Biomedical Sciences, University of Bradford, Richmond Road, Bradford BD7 1DP, West Yorkshire, UK

关键词: Platelet;    Protein nitration;    Tyrosine phosphorylation;    Cyclic guanosine monophosphate;   

DOI  :  10.1016/S0014-5793(01)03279-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Peroxynitrite at low concentrations (3–10 μM) inhibited agonist-induced platelet aggregation by a mechanism not dependent on the formation of cyclic guanosine monophosphate. Platelets recovered completely from peroxynitrite-induced inhibition within 30 min. Peroxynitrite induced nitration of cytosolic proteins, but this diminished to near basal levels within 60 min of exposure to the oxidant. During this period there was a reduction in tyrosine phosphorylation of specific proteins such as syk, but this was not due to direct nitration of these same proteins. The inhibition of phosphorylation was reversible with platelet proteins recovering the ability to be phosphorylated within 15 min of exposure to peroxynitrite. Conversely, peroxynitrite increased phosphorylation of other proteins, but again these events were not directly linked to nitration. Nitration may affect the phosphorylation of tyrosine residues in a number of proteins, but by an indirect route, possibly by acting on proteins upstream in the signalling cascades. We suggest that low concentrations of peroxynitrite reversibly inhibit platelet aggregation by preventing the phosphorylation of key signalling proteins.

【 授权许可】

Unknown