| First Author | Grkovich A | Year | 2009 |
| Journal | Biochim Biophys Acta | Volume | 1791 |
| Issue | 10 | Pages | 975-82 |
| PubMed ID | 19230851 | Mgi Jnum | J:153375 |
| Mgi Id | MGI:4365319 | Doi | 10.1016/j.bbalip.2009.02.002 |
| Citation | Grkovich A, et al. (2009) TLR-4 mediated group IVA phospholipase A(2) activation is phosphatidic acid phosphohydrolase 1 and protein kinase C dependent. Biochim Biophys Acta 1791(10):975-82 |
| abstractText | Group IVA phospholipase A(2) (GIVA PLA(2)) catalyzes the release of arachidonic acid (AA) from the sn-2 position of glycerophospholipids. AA is then further metabolized into terminal signaling molecules including numerous prostaglandins. We have now demonstrated the involvement of phosphatidic acid phosphohydrolase 1 (PAP-1) and protein kinase C (PKC) in the Toll-like receptor-4 (TLR-4) activation of GIVA PLA(2). We also studied the effect of PAP-1 and PKC on Ca(+2) induced and synergy enhanced GIVA PLA(2) activation. We observed that the AA release induced by exposure of RAW 264.7 macrophages to the TLR-4 specific agonist Kdo(2)-Lipid A is blocked by the PAP-1 inhibitors bromoenol lactone (BEL) and propranolol as well as the PKC inhibitor Ro 31-8220; however these inhibitors did not reduce AA release stimulated by Ca(+2) influx induced by the P2X7 purinergic receptor agonist ATP. Additionally, stimulation of cells with diacylglycerol (DAG), the product of PAP-1 mediated hydrolysis, initiated AA release from unstimulated cells as well as restored normal AA release from cells treated with PAP-1 inhibitors. Finally, neither PAP-1 nor PKC inhibition reduced GIVA PLA(2) synergistic activation by stimulation with Kdo(2)-Lipid A and ATP. |
