Diazoxide and N omega-nitro-L-arginine counteracted A beta 1-42-induced cytotoxicity.
K(+) channel openers can activate K channels and have been shown to protect cultured neurons against excitotoxicity. Our study showed that diazoxide, a K(+) channel opener, could counteract the effects of A beta(1-42) and protect cells from A beta(1-42)-induced the increasing of mitochondrial membrane potential and the associated increase in intracellular reactive oxygen species levels; an inducible nitric oxide synthase inhibitor, N omega-nitro-L-arginine could protect cells from A beta(1-42)-induced the increasing of both mitochondrial membrane potential and intracellular reactive oxygen species levels. A 24 h exposure to A beta(1-42) did not result in apoptosis, suggesting that the increase in both mitochondrial membrane potential and reactive oxygen species levels preceded cell apoptosis or death.
Ma
Guozhao
G
Department of Neurology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China.
Chen
Shengdi
S
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003981:Diazoxide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D019335:Nitroarginine / Q000494:pharmacology*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000633:toxicity*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D019335:Nitroarginine; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D003981:Diazoxide