Silica Induced Phospholipase D (PLD) Activation in Rat2 Fibroblasts

Abstract

To define the effect of silica on the stimulator of signaling pathway, we studied the phospholipase D (PLD) activity in the Rat2 fibroblasts. Silica stimulated the accumulation of labeled [3H] phosphatidylethanol([3H] PEt) in a time- and concentration-dependent manner. This Silica-induced PLD activity was partially attenuated by the pretreatment with U73122 (phospholipase C inhibitor), genistein (protein tyrosine kinase inhibitor), PD 98056 (MEK inhibitor) and mepacrine (phospholipase A2 inhibitor). But, sphingosine (protein kinase C inhibitor) and DPI (NADPH reductase inhibitor) had not effect the PLD activity. Silica also increased the PLA2 activity about four fold, which imply that the PLD activity is more influenced by the mobilization of PLA2 than other signaling mediators. The PLD activity also partially inhibited calcium chelator EGTA or/and BAPTA/AM compared to silica. Finally, we concluded that a silica-stimulated phospholipase D activity is present in the Rat2 fibroblasts and is modulated by combination of various signaling mediators.