title: Involvement of phospholipase D in oxidative stress-induced necrosis of vascular smooth muscle cells.
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.
authors.affiliation: Department of Biochemistry, College of Medicine and Research Institute for Genetic Engineering, Chungbuk National University, Cheongju, South Korea.
authors.forename: E Y
authors.initials: EY
authors.lastname: Shin
authors.forename: D S
authors.initials: DS
authors.lastname: Min
authors.forename: J C
authors.initials: JC
authors.lastname: Shin
authors.forename: K S
authors.initials: KS
authors.lastname: Shin
authors.forename: M S
authors.initials: MS
authors.lastname: Hyun
authors.forename: K S
authors.initials: KS
authors.lastname: Ha
authors.forename: H S
authors.initials: HS
authors.lastname: Kim
authors.forename: H Y
authors.initials: HY
authors.lastname: Ahn
authors.forename: E G
authors.initials: EG
authors.lastname: Kim
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D000440:Butanols / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D009336:Necrosis; D018384:Oxidative Stress / Q000187:drug effects; D010739:Phospholipase D / Q000378:metabolism*; D051381:Rats; D013997:Time Factors; D014638:Vanadates / Q000494:pharmacology
chemical_list: D000440:Butanols; C076715:pervanadate; D014638:Vanadates; D006861:Hydrogen Peroxide; D010739:Phospholipase D; D002118:Calcium