Journal: Redox Report : Communications in Free Radical Research
Article Title: Phospholipase C-γ2 via p38 and ERK1/2 MAP kinase mediates diperoxovanadate-asparagine induced human platelet aggregation and sCD40L release
Figure Lengend Snippet: Schematic illustration of DPV-Asn-induced oxidative stress in platelets causing aggregation and sCD40L release. The model depicts that catalase-tolerant peroxide DPV-Asn mediates sequential induction of a signaling cascade in platelets, chiefly regulated by PLC-γ2, which apparently played a central role in upregulating dense granule secretion, calcium influx, p38 and ERK1/2 MAP kinase phosphorylation, and subsequently directed COX activation and enhanced TxA 2 generation to further amplify platelet aggregation and thrombus formation. DPV-Asn further augments GPIIbIIIa-dependent release of proinflammatory cytokine sCD40L, thereby exhibiting a thrombo-inflammatory phenotype. DPV-Asn, diperoxovanadate-asparagine; ROS, reactive oxygen species; NAC, N -acetyl cysteine; AA, arachidonic acid; COX, cycloxygenase; TxA 2 , thromboxane A 2 ; TP, thromboxane-prostanoid receptor.
Article Snippet: Results Platelet aggregation induced by DPV-Asn was chiefly regulated by dense granule secretion, thromboxane A2 (TxA2 ) generation, intra-platelet [Ca2+ ] influx, GPIIbIIIa activation and sCD40L release, which were significantly reduced in presence of U73122 (PLC inhibitor), aspirin (COX), SB203580 (p38 inhibitor), and PD98059 (ERK inhibitor).
Techniques: Planar Chromatography, Activation Assay