Superoxide is responsible for apoptosis in rat vascular smooth muscle cells induced by alpha-tocopheryl hemisuccinate.
We investigated the mechanism of cell toxicity of alpha-tocopheryl hemisuccinate (TS). TS concentration- and time-dependently induced the lactate dehydrogenase release and DNA fragmentation of rat vascular smooth muscle cells (VSMC). Exogenous addition of superoxide dismutase, but not catalase, significantly inhibited the cell toxicity of TS. The NADPH-dependent oxidase activity of VSMC was stimulated by TS treatment. The cell toxicity of TS was inhibited by NADPH oxidase inhibitor 4-(2-aminoethyl)-benzenesulfonyl fluoride. Consequently, TS-induced apoptosis of VSMC was suggested to be caused by exogenous O(2)(-) generated via the oxidase system activated with TS.
Kogure
K
K
Faculty of Pharmaceutical Sciences, University of Tokushima, Shomachi-1, Tokushima 770-8505, Japan.
Morita
M
M
Nakashima
S
S
Hama
S
S
Tokumura
A
A
Fukuzawa
K
K
D000818:Animals; D017209:Apoptosis; D001205:Ascorbic Acid; D002374:Catalase; D002478:Cells, Cultured; D003574:Cytochrome c Group / Q000737:chemistry; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010100:Oxygen / Q000032:analysis; D051381:Rats; D013482:Superoxide Dismutase; D013481:Superoxides / Q000032:analysis / Q000378:metabolism*; D024505:Tocopherols; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000633:toxicity*
D003574:Cytochrome c Group; D013481:Superoxides; D014810:Vitamin E; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D001205:Ascorbic Acid; D024505:Tocopherols; D010100:Oxygen