Peroxynitrite-induced toxicity in cultured astrocytes.
The exposure of cultured astrocytes to peroxynitrite (ONOO-) for 40 min resulted in a concentration-dependent increase in the release of lactate dehydrogenase from the cells into the bathing medium over the following 24 h. Control experiments showed that the breakdown products of ONOO- contribute, to some extent, to its ability to cause cell death but that the drug vehicle (0.3 M NaOH), which increased the pH of the bathing medium to 9.4, had little effect. The cytotoxic action of ONOO- was mimicked by 3-morpholinosydnonimine (SIN-1) which liberates both nitric oxide (NO) and superoxide but not by S-nitrosoglutathione which liberates only NO. SIN-1-induced cytotoxicity was reversed in a concentration-dependent manner by superoxide dismutase and attenuated by haemoglobin suggesting that the effect of SIN-1 is due, at least in part, to the formation of ONOO-.
Amin
N
N
Pharmacology Department, The School of Pharmacy, London, UK.
Pearce
B
B
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000633:toxicity; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D007770:L-Lactate Dehydrogenase; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000633:toxicity; D009566:Nitrates / Q000633:toxicity*; D009569:Nitric Oxide / Q000378:metabolism*; D009603:Nitroso Compounds / Q000494:pharmacology; D016877:Oxidants / Q000633:toxicity*; D051381:Rats; D026422:S-Nitrosoglutathione; D013481:Superoxides / Q000378:metabolism
D004791:Enzyme Inhibitors; D009566:Nitrates; D009603:Nitroso Compounds; D016877:Oxidants; D013481:Superoxides; C039642:peroxynitric acid; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; C002385:linsidomine; D008981:Molsidomine; D007770:L-Lactate Dehydrogenase; D005978:Glutathione