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Nitrolinoleate inhibits platelet activation by attenuating calcium mobilization and inducing phosphorylation of vasodilator-stimulated phosphoprotein through elevation of cAMP.
J Biol Chem. 2002 Feb 22; 277(8):5832-40.JB

Abstract

Reactive species formed from nitric oxide (NO) nitrate unsaturated fatty acids such as linoleate (LA) to nitrated derivatives including nitrolinoleate (LNO(2)). The effect of LNO(2) on human platelets was examined to define how nitrated lipids might behave in vivo. LNO(2), but not LA or 3-nitrotyrosine, dose dependently (0.5-10 microm) inhibited thrombin-mediated aggregation of washed human platelets, with concomitant attenuation of P-selectin expression and selective phosphorylation of VASP at the cAMP-dependent protein kinase selective site, serine 157. LNO(2) caused slight mobilization of calcium (Ca(2+)) from intracellular stores but significantly inhibited subsequent thrombin-stimulated Ca(2+) elevations. LNO(2) did not elevate platelet cGMP, and its effects were not blocked with inhibitors of NO signaling (oxyhemoglobin, 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one. 2-fold elevations in cAMP were found following LNO(2) treatment of platelets, and the adenylyl cyclase inhibitors 2',5'-dideoxyadenosine and SQ22536 partially restored thrombin-stimulated aggregation. Finally, LNO(2) significantly inhibited cAMP hydrolysis to AMP by platelet lysates. These data implicate cAMP in the anti-aggregatory action of LNO(2). The platelet inhibitory actions of LNO(2) indicate that nitration reactions that occur following NO generation in an oxidizing environment can alter the activity of lipids and lend insight into mechanisms by which NO-derived species may modulate the progression of vascular injury.

Authors+Show Affiliations

Department of Medical Biochemistry, University of Wales College of Medicine, Heath Park, Cardiff CF4 4XN, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11748216

Citation

Coles, Barbara, et al. "Nitrolinoleate Inhibits Platelet Activation By Attenuating Calcium Mobilization and Inducing Phosphorylation of Vasodilator-stimulated Phosphoprotein Through Elevation of CAMP." The Journal of Biological Chemistry, vol. 277, no. 8, 2002, pp. 5832-40.
Coles B, Bloodsworth A, Eiserich JP, et al. Nitrolinoleate inhibits platelet activation by attenuating calcium mobilization and inducing phosphorylation of vasodilator-stimulated phosphoprotein through elevation of cAMP. J Biol Chem. 2002;277(8):5832-40.
Coles, B., Bloodsworth, A., Eiserich, J. P., Coffey, M. J., McLoughlin, R. M., Giddings, J. C., Lewis, M. J., Haslam, R. J., Freeman, B. A., & O'Donnell, V. B. (2002). Nitrolinoleate inhibits platelet activation by attenuating calcium mobilization and inducing phosphorylation of vasodilator-stimulated phosphoprotein through elevation of cAMP. The Journal of Biological Chemistry, 277(8), 5832-40.
Coles B, et al. Nitrolinoleate Inhibits Platelet Activation By Attenuating Calcium Mobilization and Inducing Phosphorylation of Vasodilator-stimulated Phosphoprotein Through Elevation of CAMP. J Biol Chem. 2002 Feb 22;277(8):5832-40. PubMed PMID: 11748216.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nitrolinoleate inhibits platelet activation by attenuating calcium mobilization and inducing phosphorylation of vasodilator-stimulated phosphoprotein through elevation of cAMP. AU - Coles,Barbara, AU - Bloodsworth,Allison, AU - Eiserich,Jason P, AU - Coffey,Marcus J, AU - McLoughlin,Rachel M, AU - Giddings,John C, AU - Lewis,Malcolm J, AU - Haslam,Richard J, AU - Freeman,Bruce A, AU - O'Donnell,Valerie B, Y1 - 2001/12/17/ PY - 2001/12/19/pubmed PY - 2002/4/25/medline PY - 2001/12/19/entrez SP - 5832 EP - 40 JF - The Journal of biological chemistry JO - J Biol Chem VL - 277 IS - 8 N2 - Reactive species formed from nitric oxide (NO) nitrate unsaturated fatty acids such as linoleate (LA) to nitrated derivatives including nitrolinoleate (LNO(2)). The effect of LNO(2) on human platelets was examined to define how nitrated lipids might behave in vivo. LNO(2), but not LA or 3-nitrotyrosine, dose dependently (0.5-10 microm) inhibited thrombin-mediated aggregation of washed human platelets, with concomitant attenuation of P-selectin expression and selective phosphorylation of VASP at the cAMP-dependent protein kinase selective site, serine 157. LNO(2) caused slight mobilization of calcium (Ca(2+)) from intracellular stores but significantly inhibited subsequent thrombin-stimulated Ca(2+) elevations. LNO(2) did not elevate platelet cGMP, and its effects were not blocked with inhibitors of NO signaling (oxyhemoglobin, 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one. 2-fold elevations in cAMP were found following LNO(2) treatment of platelets, and the adenylyl cyclase inhibitors 2',5'-dideoxyadenosine and SQ22536 partially restored thrombin-stimulated aggregation. Finally, LNO(2) significantly inhibited cAMP hydrolysis to AMP by platelet lysates. These data implicate cAMP in the anti-aggregatory action of LNO(2). The platelet inhibitory actions of LNO(2) indicate that nitration reactions that occur following NO generation in an oxidizing environment can alter the activity of lipids and lend insight into mechanisms by which NO-derived species may modulate the progression of vascular injury. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/11748216/Nitrolinoleate_inhibits_platelet_activation_by_attenuating_calcium_mobilization_and_inducing_phosphorylation_of_vasodilator_stimulated_phosphoprotein_through_elevation_of_cAMP_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(19)82347-5 DB - PRIME DP - Unbound Medicine ER -