Nitric oxide and superoxide, a deadly cocktail.

ABSTRACT

Free radicals and oxidants may have contrasting effects on cells. Nitric oxide is a cellular messenger that acts by several mechanisms, including activation of soluble guanylate cyclase, nitrosylation of thiols, and formation of peroxynitrite. The action of nitric oxide depends on oxidative conditions in the cell. In motor neurons, nitric oxide enhances brain-derived neurotrophic factor effects by stimulation of cGMP production. In the absence of trophic factors, nitric oxide induces motor neuron apoptosis by reacting with superoxide to form peroxynitrite. The mechanism of induction of motor neuron apoptosis by the formation of peroxynitrite is more complicated than simply the formation of a strong oxidant and it also involves decreased formation of cGMP.