Oxidative stress and inhibition of oxidative phosphorylation induced by peroxynitrite and nitrite in rat brain subcellular fractions.
Nitrite and nitrate, two endogenous oxides of nitrogen, are toxic in vivo. Furthermore, the reaction of superoxide (produced by all aerobic cells) with nitric oxide (NO) generates peroxynitrite, a potent oxidizing agent, that can cause biological oxidative stress. Using subcellular fractions from rat brain hemispheres we studied oxidative stress induced by these nitrogen compounds with special emphasis on nitrite. The consumption of Vitamin C (ascorbate) and Vitamin E (alpha tocopherol), two of the important nutritional antioxidants, was followed in synaptosomes (nerve-ending particles) and mitochondria along with changes in parameters of mitochondrial oxidative phosphorylation. Nitrite, but not nitrate, oxidized ascorbate without oxidizing alpha tocopherol in both synaptosomes and mitochondria whereas peroxynitrite oxidized both ascorbate and alpha tocopherol. Functionally, both nitrite and peroxynitrite inhibited mitochondrial oxidative phosphorylation. Nitrite was less potent than peroxynitrite when the effects of equal concentrations of the two were compared. However, since nitrite is much more stable than peroxynitrite the impact of nitrite as an oxidant in vivo could be as much or even more significant than peroxynitrite. Nitrate would not have similar action unless it is reduced to nitrite. It is possible that nitrite may impair oxidative phosphorylation through modulating levels of nitric oxide, changing the activity of heme proteins or a mild uncoupling of mitochondria.
Vatassery
Govind T
GT
Research Service and GRECC, VA Medical Center, Minneapolis, MN 55417, USA. vatas001@tc.umn.edu
SantaCruz
Karen S
KS
DeMaster
Eugene G
EG
Quach
Hung T
HT
Smith
W Ed
WE
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D009573:Nitrites / Q000494:pharmacology*; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D030421:Peroxynitrous Acid / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism
D009573:Nitrites; D030421:Peroxynitrous Acid