Nitric oxide (NO) is a free radical that regulates blood flow and many other physiological processes. Constitutive production of nitric oxide by endothelial nitric oxide synthase (eNOS) also prevents unwanted adhesion and activation of circulating blood platelets and leukocytes, which is crucial for haemostasis and regulation of inflammatory responses. Formation of 3-nitrotyrosine and the S-nitrosylation of free cysteine residues within proteins are important posttranslational protein modifications that rely on nitric oxide production. S-nitrosylation is emerging as a key mechanism by which low constitutive NO production reversibly regulates endothelial and platelet secretory events. High amounts of NO are particularly generated under inflammatory conditions and may have consequences for platelet functioning.
Aim
To determine the role of NO-dependent protein modifications in platelet functioning and to identify protein targets at steady state and under inflammatory conditions (In collaboration with Harry Ischiropoulos, Philadelphia, USA).
References:
Fibrinogen beta -chain tyrosine nitration is a prothrombotic risk factor I. Parastatidis, L.M. Thomson, A. Burke, I. Chernysh, C. Nagaswami, J. Visser, S. Stamer, D.C. Liebler, G. Koliakos, H.F.G. Heijnen, G.A. FitzGerald, J.W. Weisel, H. Ischiropoulos. 2008. Epub ahead of print sept. J. Biol. Chem.
Increased Protein Nitration Burden in the Atherosclerotic Lesions and Plasma of Apolipoprotein A-I-Deficient Mice. Parastatidis I, Thomson L, Fries DM, Moore RE, Tohyama J, Fu X, Hazen SL, Heijnen HF, Dennehy MK, Liebler DC, Rader DJ, Ischiropoulos H. Circ. Res. 101:368-76, 2007.
Identification of S-nitrosylation motifs by site-specific mapping of the S-nitrosocysteine proteome in human vascular smooth muscle cells. Todd M. Greco, Roberto Hodara, Ioannis Parastatidis, Harry F. G. Heijnen, Michelle K. Dennehy, Daniel C. Liebler, and Harry Ischiropoulos. 2006. Proc. Nat. Acad. Sci.103:7420-7425.
Subcellular localization of tyrosine-nitrated proteins is dictated by reactive oxygen species generating enzymes and by proximity to nitric oxide synthase. H.F.G. Heijnen, E. van Donselaar, J.W. Slot, D.M. Fries, B. Blachard-Fillion, R. Hodara, R. Lightfoot, M. Polydoro, D. Spielberg, L. Thomson, E.A. Regan, J. Crapo, H. Ischiropoulos. 2006. Free Rad. Biol. Med. 40:1903-1913.
Expression of inducible nitric oxide synthase and intracellular protein tyrosine nitration in vascular smooth muscle cells: Role of reactive oxygen species. Fries, D.M., E. Paxinou, M. Themistocleous, E. Swanberg, K.K. Griendling, D. Salvemini, J.W. Slot, H. F. Heijnen, S.L. Hazen, and H. Ischiropoulos. 2003.J. Biol. Chem. 278: 22904-22907.