Cobalt prevents nitric oxide-induced apoptotic motoneuron death in vitro.
We studied the mechanism of nitric oxide (NO) toxicity in cultured rat spinal motoneurons. Treatment with the NO donor NOC-18 (NOC) resulted in slow motoneuron death, ending in apoptosis. The observed motoneuron death was completely prevented by hemoglobin. Treatment with inhibitors of the known intracellular targets of NO, soluble guanylate cyclase, polyADP-ribose polymerase (PARP) and superoxide, did not result in any significant protection against NOC-induced motoneuron death. ATP levels were reduced as soon as 3 h after the start of NOC treatment, suggesting a direct inhibition of cellular energy production. NOC toxicity could be blocked by the general voltage-gated calcium channel blocker cobalt, but not by specific blockers of various subtypes of calcium channels.
Kaal
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Laboratory for Experimental Neurology, University Medical Centre Utrecht, The Netherlands.
Kil
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Sodaar
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Joosten
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Bär
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D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000506:poisoning; D002478:Cells, Cultured; D003035:Cobalt / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism; D004594:Electrophysiology; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D009410:Nerve Degeneration / Q000503:physiopathology; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D011506:Proteins / Q000378:metabolism; D051381:Rats
C093285:NOC 18; D009566:Nitrates; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D011506:Proteins; C039642:peroxynitric acid; D009569:Nitric Oxide; D003035:Cobalt; D000255:Adenosine Triphosphate; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D006152:Cyclic GMP; D002118:Calcium