Peroxynitrite induces apoptosis in canine cerebral vascular muscle cells: possible relation to neurodegenerative diseases and strokes.
Considerable evidence is accumulating to suggest that in vivo formation of free radicals in the brain, such as peroxynitrite (ONOO-), and programmed cell death (i.e. apoptosis) play important roles in neurodegeneration and stroke. However, it is not known whether ONOO- can induce apoptosis in cerebral vascular smooth muscle cells (CVSMCs). The present study was designed to determine whether or not canine CVSMCs undergo apoptosis following treatment with ONOO-. Direct exposure of canine CVSMCs to ONOO- induced apoptosis in a concentration-dependent manner, as confirmed by means of fluorescence staining, TdT-mediated dUTP nick-end labeling and comet assays. Peroxynitrite treatment resulted in an elevation of [Ca2+]i in the CVSMCs. Peroxynitrite-induced apoptosis may thus be brought about by activation of Ca2+-dependent endonucleases. Although the precise mechanisms by which peroxynitrite induces apoptosis need to be further investigated, the present findings could be used to suggest that ONOO- formation in the brain may play important roles in neurodegenerative processes and strokes via detrimental actions on cerebral microvessels and blood flow.
Li
Jianfeng
J
Department of Physiology and Pharmacology, State University of New York Downstate Medical Center, Health Science Center at Brooklyn, 450 Clarkson Avenue, Brooklyn, NY 11203, USA.
Su
Jialin
J
Li
Wenyan
W
Liu
Weimin
W
Altura
Bella T
BT
Altura
Burton M
BM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002536:Cerebral Arteries / Q000187:drug effects / Q000473:pathology; D002540:Cerebral Cortex / Q000098:blood supply; D020552:Comet Assay; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D020287:In Situ Nick-End Labeling; D008297:Male; D008856:Microscopy, Fluorescence; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology*; D019636:Neurodegenerative Diseases / Q000473:pathology; D030421:Peroxynitrous Acid / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D020521:Stroke / Q000473:pathology
D017382:Reactive Oxygen Species; D030421:Peroxynitrous Acid; D002118:Calcium