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 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.
Shin
E Y
EY
Department of Biochemistry, College of Medicine and Research Institute for Genetic Engineering, Chungbuk National University, Cheongju, South Korea.
Min
D S
DS
Shin
J C
JC
Shin
K S
KS
Hyun
M S
MS
Ha
K S
KS
Kim
H S
HS
Ahn
H Y
HY
Kim
E G
EG
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
D000440:Butanols; C076715:pervanadate; D014638:Vanadates; D006861:Hydrogen Peroxide; D010739:Phospholipase D; D002118:Calcium