Influence of nitric oxide on cellular and mitochondrial integrity in oxidatively stressed astrocytes

Astrocytes provide protection and trophic support to neurons, but like neur ons are vulnerable to oxidative stress. Decreased function of astrocytes re sulting from oxidative stress could contribute to neurodegeneration, Our go al is to understand the intracellular events associated with oxidative stre ss in astrocytes. Because nitric oxide (NO.) has been implicated as a contr ibutor to oxidative stress in the brain, we examined in this study whether NO. contributed to oxidative stress in astrocytes, Stimulation of NO. decre ases superoxide levels, preserves mitochondrial membrane potential, and dec reases mitochondrial swelling in astrocytes treated with peroxide, Chelatio n of NO. is associated with increased cell death, mitochondrial swelling, a nd loss of mitochondrial membrane potential, in response to peroxide treatm ent. Peroxide treatment increased intracellular calcium and the peroxide-in duced changes in intracellular calcium were not altered in response to NO.. Iron-loading increases peroxide-induced oxidative stress in astrocytes, bu t induction of NO. limited the iron effect, suggesting an interaction betwe en iron and NO.. These data suggest endogenously produced NO. protects astr ocytes from oxidative stress, perhaps by preserving mitochondrial function. J, Neurosci, Res. 56:166-176, 1999. (C) 1999 Wiley-Liss, Inc.