Calcium dependency of prostaglandin E2 production in rat glomerular mesangial cells. Evidence that protein kinase C modulates the Ca2+-dependent activation of phospholipase A2.

Abstract

Calcium has been implicated as an important factor in prostaglandin production. Phospholipase A2, the enzyme believed to be rate limiting for prostaglandin synthesis, is stimulated by Ca2+; however, the levels of Ca2' necessary to stimulate phospholipase A2 in cell-free systems are higher than levels achieved in intact cells in

Characterization of eicosanoid synthesis in a genetic ablation model of ceramide kinase

“…In this study, we have demonstrated that CERK-derived C1P is instrumental in the production of eicosanoids, corroborating our previous studies illustrating that siRNA downregulation of CERK blocks the release AA by inhibiting Eicosanoid synthesis in CERK ؊ / ؊ cells 1843 kinase C, which has been strongly linked to cPLA 2 ␣ activation (50)(51)(52)(53). This activation may or may not be dependent on C1P, and unpublished fi ndings from our laboratory show that a DAG lipase inhibitor is a dramatic stimulator of eicosanoid synthesis without the requirement of C1P.…”

Role of cytosolic calcium-independent plasmalogen-selective phospholipase A2 in hypoxic injury to rabbit proximal tubules.

“…In addition, the increase in plasmalogen-selective PLA2 during hypoxia measured in the absence or presence of calcium was confined to the cytosolic compartment with minimal change in membrane-associated activity. Accordingly, there is no significant translocation of enzyme activity, a characteristic of the human monocytic and rat kidney PLA2 enzyme activity using diacylglycerophospholipid substrates (21)(22)(23)(24)(25)(26)(27)(28). Although Ca2+ is not required for catalytic activity and calcium-dependent translocation does not occur, it is still possible that calcium-dependent mechanisms such as protein kinase C-mediated phosphorylation of PLA2 may play a role in the activation of cytosolic plasmalogen-selective PLA2 in rabbit proximal tubules during hypoxia.…”

Cross-talk between Cytosolic Phospholipase A2α (cPLA2α) and Secretory Phospholipase A2 (sPLA2) in Hydrogen Peroxide-induced Arachidonic Acid Release in Murine Mesangial Cells

“…The PKC inhibitor GF 109203x is known to be more selective for the ␣ isoform than for other PKC isoforms (80,81), suggesting the relevance of this isoform. A number of years ago, we had shown that agents that activate PKC could activate high molecular mass soluble PLA 2 activity in mesangial cells as long as there was an increase in [Ca 2ϩ ] i (82,83). Subsequent to the identification of this activity as cPLA 2 ␣, other investigators have reported that PKC is involved in the regulation of cPLA 2 ␣ (29, 31, 79, 84 -86).…”