Neuroprotective effect of cyclic GMP against radical-induced toxicity in cultured spinal motor neurons

We have previously reported that nitric oxide-related cyclic guanosine-3',5 '-monophosphate (GMP) protected spinal nonmotor neurons, but not motor neur ons against chronic glutamate-induced toxicity, which is associated with se lective motor neuronal death after glutamate stress. In this report, we inv estigated the effect of cyclic GMP against reactive oxygen species (ROS)-in duced toxicity in cultured neurons from embryonic rat spinal cords. Pretrea tment with a cGMP analogue, 8-bromoguanosine monophosphate (8br-cGMP), for 12-24 hours protected both spinal motor neurons and nonmotor neurons agains t injury induced by either hydrogen peroxide (H2O2), or a glutathione deple tor, L-buthionine-[S,R]-sulfoximine (BSO). This protective effect was rever sed by coadministration with the cGMP-dependent protein kinase (PKG) inhibi tor Arg-Lys-Arg-Ala-Arg-Lys-Glu. interestingly, when cultures were exposed to BSO for 24 hours to allow irreversible inhibition of glutathione synthes is, 8br-cGMP protected only nonmotor neurons. Our results indicate that cGM P attenuates oxidative injury to cultured spinal neurons, in a mechanism as sociated with glutathione synthesis. (C) 2000 Wiley-Liss, Inc.