Involvement of phospholipase D in oxidative stress-induced necrosis of vascular smooth muscle cells. |
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| Authors: | E Y Shin D S Min J C Shin K S Shin M S Hyun K S Ha H S Kim H Y Ahn E G Kim |
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| Affiliation: | Department of Biochemistry, College of Medicine and Research Institute for Genetic Engineering, Chungbuk National University, Cheongju, South Korea. |
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| 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 Ca(2+). Removal of extracellular Ca(2+) 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 Ca(2+) toxicity. |
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