EPC-K1 attenuates peroxynitrite-induced apoptosis in cerebellar granule cells.
Apoptosis induced by peroxynitrite in cultured cerebellar granule cells was confirmed morphologically by chromatin condensation and biochemically by DNA laddering. A 30 min exposure to peroxynitrite (10 microM) initiated oxidative stress, which caused the formation of thiobarbituric acid-reactive substances (TBARS) and the alteration of cell membrane fluidity. Peroxynitrite treatment also caused ATP decrease and thus activated the apoptotic program. Pre-treating cells with antioxidant EPC-K1 (L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H -1- benzopyran-6-yl-hydrogen phosphate] potasium salt), a new water-soluble derivative of vitamin C and vitamin E, attenuated oxidative injury and prevents cells from apoptosis. The results suggest that EPC-K1 might be used as a potential therapeutic agent for diseases associated with NO/ONOO(-)-mediated neuronal injury.
Institute of Biophysics, Academia Sinica, Beijing, China.
T
T
Wei
C
C
Chen
B
B
Zhao
W
W
Xin
A
A
Mori
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002470:Cell Survival; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D053938:DNA Fragmentation; D015227:Lipid Peroxidation; D008560:Membrane Fluidity / Q000187:drug effects; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009566:Nitrates / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology
D000975:Antioxidants; D009566:Nitrates; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; C039642:peroxynitric acid; C066638:potassium ascorbyl tocopheryl phosphate; D000255:Adenosine Triphosphate; D001205:Ascorbic Acid