Homocysteine acts via nitric oxide synthase to sensitize the crayfish neuromuscular junction to hydrogen-peroxide-induced oxidative damage

Abstract

Oxidative stress may be a significant source of damage in many neurodegenerative disorders, including amyotrophic lateral sclerosis. Reactive oxygen species such as hydrogen peroxide cause oxidative stress. We hypothesized that: (1) hydrogen-peroxide-induced oxidative damage would decrease excitatory junction potential amplitude at the crayfish neuromuscular junction, (2) incubation in homocysteine would enhance the amplitude decrease caused by hydrogen peroxide, and (3) inhibiting nitric oxide synthase would negate the effect of homocysteine. We used intracellular recording to measure excitatory junction potential amplitudes in each of these conditions before and after the neuromuscular junction was exposed to hydrogen peroxide for twenty minutes. Our findings support these hypotheses, suggesting that homocysteine sensitizes neurons to oxidative damage via stimulation of nitric oxide synthase.