Hypoxia and Hyperoxia Both Increase Superoxide Production in Nucleus Tractus Solitarius (NTS) Neurons in Rat Brain Tissue Slices
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Maintaining brain slices in 95%O2 produces hyperoxia, oxidative stress and increased cell death, whereas decreasing control O2 to 20-40% significantly decreases both oxidative stress and cell death (J. Neurophysiol. 98:1030-41, 2007) and maintains neuronal excitability (Matott et al., this meeting). In this study, beginning at 20-40%O2, we tested the hypothesis that acute hyperoxia and hypoxia both increase the rate of superoxide (·O2-) production in NTS neurons. Medullary slices (400µm, weaned rats, 36-37oC) were maintained using 2-sided superfusion. Intracellular ·O2- production was measured using dihydroethidium (DHE, 2.5µM) added to the superfusate. The rate of ·O2- production (fluorescence intensity units/min, FIU/min) increased during hypoxia (40/20%(0%O2) and was blocked by myxothiazol (10µM; inhibits ·O2- produced by mitochondrial Complex III). ·O2- production also increased during hyperoxia (20(95%O2), but to a lesser extent than during hypoxia, and was not blocked by myxothiazol. We propose that NTS neurons undergo redox stimulation and/or stress via increased ·O2- production during both hypoxia (Complex III) and hyperoxia (Complex I ?). We also hypothesize that the smaller increase in FIUDHE/min during hyperoxia reflects increased production of ·NO during hyperoxia, which reacts with ·O2- (and thus consumes ·O2-) to yield peroxynitrite. ONR N000140710890, NIH R01 HL 56683-10.
Dean, J. B.,
Landon, C. S.,
D'Agostino, D. P.,
& Putnam, R. W.
(2009). Hypoxia and Hyperoxia Both Increase Superoxide Production in Nucleus Tractus Solitarius (NTS) Neurons in Rat Brain Tissue Slices. The FASEB Journal, 23 (Meeting Abstract Supplement).
Presented at the 2009 Federation of American Societies for Experimental Biology (FASEB) Science Research Conference.
Presentation Number 1038.8.