Influence of nitric oxide on cellular and mitochondrial integrity in oxidatively stressed astrocytes.
Astrocytes provide protection and trophic support to neurons, but like neurons are vulnerable to oxidative stress. Decreased function of astrocytes resulting from oxidative stress could contribute to neurodegeneration. Our goal is to understand the intracellular events associated with oxidative stress in astrocytes. Because nitric oxide (NO) has been implicated as a contributor to oxidative stress in the brain, we examined in this study whether NO contributed to oxidative stress in astrocytes. Stimulation of NO decreases superoxide levels, preserves mitochondrial membrane potential, and decreases mitochondrial swelling in astrocytes treated with peroxide. Chelation of NO is associated with increased cell death, mitochondrial swelling, and loss of mitochondrial membrane potential, in response to peroxide treatment. Peroxide treatment increased intracellular calcium and the peroxide-induced changes in intracellular calcium were not altered in response to NO. Iron-loading increases peroxide-induced oxidative stress in astrocytes, but induction of NO limited the iron effect, suggesting an interaction between iron and NO. These data suggest endogenously produced NO protects astrocytes from oxidative stress, perhaps by preserving mitochondrial function.
Robb
S J
SJ
George M. Leader Family Laboratory, Department of Neuroscience and Anatomy, The Pennsylvania State University College of Medicine, M.S. Hershey Medical Center, Hershey 17033, USA.
Gaspers
L D
LD
Wright
K J
KJ
Thomas
A P
AP
Connor
J R
JR
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D003497:Cyclic N-Oxides / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
D000970:Antineoplastic Agents; D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D007093:Imidazoles; D008070:Lipopolysaccharides; D020030:Nitric Oxide Donors; C110881:S-nitro-N-acetylpenicillamine; C079391:2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide; D009569:Nitric Oxide; D007371:Interferon-gamma; D020122:tert-Butylhydroperoxide; D007770:L-Lactate Dehydrogenase; D010396:Penicillamine