Cobalt prevents nitric oxide-induced apoptotic motoneuron death in vitro

WE studied the mechanism of nitric oxide (NO) toxicity in cultured rat spin al motoneurons. Treatment with the NO donor NOC-18 (NOC) resulted in slow m otoneuron death, ending in apoptosis. The observed motoneuron death was com pletely prevented by hemoglobin. Treatment with inhibitors of the known int racellular targets of NO, soluble guanylate cyclase, polyADP-ribose polymer ase (PARP)and superoxide, did not result in any significant protection agai nst NOC-induced motoneuron death. ATP levels were reduced as soon as 3 h af ter the start of NOC treatment, suggesting a direct inhibition of cellular energy production. NOC toxicity could be blocked by the general voltage-gat ed calcium channel blocker cobalt, but not by specific blockers of various subtypes of calcium channels. NeuroReport 10:2335-2339 (C) 1999 Lippincott Williams & Wilkins.