Involvement of phospholipase D in oxidative stress-induced necrosis of vascular smooth muscle cells

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Authors: Eun-Young Shin ; Do Sik Min ; Ji-Cheol Shin ; Kyung-Sun Shin ; Min-Soo Hyun ; Kwon-Soo Ha ; Hun-Sik Kim ; Hee-Yul Ahn ; Eung-Gook Kim

MeSH: Animals ; Aorta/cytology ; Butanols/pharmacology ; Calcium/pharmacology ; Cells, Cultured ; Dose-Response Relationship, Drug ; Enzyme Activation/drug effects ; Flow Cytometry ; Hydrogen Peroxide/pharmacology ; Muscle, Smooth, Vascular/cytology* ; Muscle, Smooth, Vascular/drug effects ; Muscle, Smooth, Vascular/enzymology* ; Necrosis ; Oxidative Stress*/drug effects ; Phospholipase D/metabolism* ; Rats ; Time Factors ; Vanadates/pharmacology

Keywords: Phospholipase D ; Pervanadate ; Necrosis ; Vascular smooth muscle cell

Abstract: Phospholipase D (PLD) has been associated with necrosis. However, it is not clear whether PLD plays a causative role in this cellular process. We investigated the role of PLD in oxidative stress-induced necrosis of vascular smooth muscle cells (VSMCs). Pervanadate (hydrogen peroxide plus orthovanadate) but not hydrogen peroxide alone activated PLD in a dose- and time-dependent manner. Exposure of VSMCs to pervanadate resulted in necrosis. Pretreatment with butan-1-ol, a PLD inhibitor, attenuated both pervanadate-induced necrosis and increase of intracellular Ca2+. Removal of extracellular Ca2+ inhibited pervanadate-induced necrosis by 50%. These results suggest that PLD activation mediates pervanadate-induced necrosis of VSMCs, which is at least partly due to Ca2+ toxicity.