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

Phospholipase D (PLD) has been associated with necrosis. However, it is not clear whether PLD plays a causative role in this cellular process. We inve stigated the role of PLD in oxidative stress-induced necrosis of vascular s mooth muscle cells (VSMCs). Pervanadate (hydrogen peroxide plus orthovanada te) but not hydrogen peroxide alone activated PLD in a dose- and time-depen dent manner. Exposure of VSMCs to pervanadate resulted in necrosis. Pretrea tment with butan-1-ol, a PLD inhibitor, attenuated both pervanadate-induced necrosis and Ca2+ increase of intracellular Ca2+. Removal of extracellular 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. (C) 2001 Federation of European Biochemi cal Societies. Published by Elsevier Science B.V. All rights reserved.