Functional Coupling between cPLA2 and COX-2 Expression Induced by ATP in Rat Vascular Smooth Muscle Cells

  • Yang, Chuen-Mao (PI)

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details


Atherosclerosis is a risk factor of morbidity and mobility, which is recognized as an inflammatory disease. Extracellular ATP has been considered as a critical modulator of inflammatory responses of the vessel resident cells including vascular smooth muscle cells (VSMC). Several lines of evidence demonstrate that activation of P2Y receptors induces breakdown of phosphoinositide, leading to activation of PKC and mobilization of intracellular Ca2+ in VSMC. Extracellular ATP also mediates activation of cPLA2 and release of PGs through activation of P2Y receptor. Several external stimuli have been shown to induce activation and up-regulation of cPLA2 mediated through activation of p42/p44 MAPK, p38 MAPK, the c-jun-N-terminal kinase (JNK), PI3K/Akt, and NF-B. Up-regulation of cPLA2 has been implicated in the pathogenesis of inflammatory diseases. Induction of COX-2 expression is also mediated through MAPKs and PI3K/NF-κB pathway, respectively. The production of eicosanoids is controlled by the availability of free arachidonic acid (AA) released by cPLA2 which was further converted by COX-2. The elevated level of eicosanoids has been shown to be implicated in vascular diseases. Our hypothesis of this proposal is that up-regulation of cPLA2 and COX-2 induced by ATP may contribute to inflammatory responses in atherosclerosis. However, the relationship of cPLA2 and COX-2 expression induced by ATP and their signal transduction pathways in VSMC remain unknown. Therefore, this proposal will be focus to investigate the mechanisms underlying the intracellular signaling involved in cPLA2 and COX-2 expression induced by ATP in VSMC. In addressing these questions, the experiments will be performed to investigate the roles of MAPKs, PI3-K/Akt, and NF-B in ATP-induced cPLA2 and COX-2 expression in VSMCs. These protein expressions occurred at transcriptional and translational levels will be investigated by cPLA2 and COX-2 promoter activity assays and and histone acetyltransferase activity in ATP-induced cPLA2 and COX-2 expression in VSMCs. An increased understanding of signal transduction pathways involved in ATP-induced cPLA2 and COX-2 expression in the vessels may be of potential therapeutic value in the treatment of inflammatory disease included artherosclerosis.

Project IDs

Project ID:PC9902-1648
External Project ID:NSC98-2320-B182-004-MY3
Effective start/end date01/08/1031/07/11


Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.