Oxidative Versus Thrombotic Stimulation of Platelets Differentially activates Signalling Pathways

Abstract

Introduction: Atherosclerosis is one of the inflammatory underlying disease associated by oxidative stress and thrombotic agents. This study aimed to evaluate the potential role of cupper oxidized low-density lipoprotein (OxLDL) and thrombin for inducing mitogen activated protein kinases (MAPKs) in platelets. Methods: Phosphorylation of P38MAPK, Jun N-terminal Kinase (JNK), and Extracellular signal-regulated kinases (ERK1/2) and P-selectin expression were determined in lysates of washed human platelets pretreated with low doses of thrombin and cu2+-OxLDL By Enzyme-linked immunosorbent assay (ELISA). Pharmacological inhibition was performed by SB203580, PD980559 and SP6000125 for P38MAPK, ERK1/2 and JNK activity, respectively. The ratio of phosphorylated to total protein was used for normalizing the phospho proteins contents of cells. Results: OxLDL and thrombin significantly and differentially increased P-selectin expression (P<0.05), P38MAPK (P<0.05) and c-JNK (P<0.05) and ERK1/2 (P<0.05) phosphorylation in platelets. SB 203580 and SP6000125 significantly decreased P-selectin expression in both oxidative (P<0.05) and thrombotic (P<0.05) activated platelets. Conclusion: Our results indicated that MAPK inhibitors can reduce atherothrombotic events via alterations in P-selectin expression suggesting that these inhibitors may be useful in the inhibition of atheroma development.

Keywords: Atherosclerosis, C-Jun N-terminal Kinase Extracellular, Signal-regulated Kinase, P38-Mitogen Activated Protein Kinase, P-selectin