Journal article
Stimulation of nitric oxide synthase in cerebral cortex due to elevated partial pressures of oxygen: an oxidative stress response
Journal of neurobiology, v 51(2), pp 85-100
May 2002
PMID: 11932951
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The purpose of this investigation was to determine the impact of elevated partial pressures of O(2) on the steady state concentration of nitric oxide ((*)NO) in the cerebral cortex. Rodents with implanted O(2)- and (*)NO-specific microelectrodes were exposed to O(2) at partial pressures from 0.2 to 2.8 atmospheres absolute (ATA) for up to 45 min. Elevations in (*)NO concentration occurred with all partial pressures above that of ambient air. In rats exposed to 2.8 ATA O(2) the increase was 692 +/- 73 nM (S.E., n = 5) over control. Changes were not associated with alterations in concentrations of nitric oxide synthase (NOS) enzymes. Based on studies with knock-out mice lacking genes for neuronal NOS (nNOS) or endothelial NOS (eNOS), nNOS activity contributed over 90% to total (*)NO elevation due to hyperoxia. Immunoprecipitation studies indicated that hyperoxia doubles the amount of nNOS associated with the molecular chaperone, heat shock protein 90 (Hsp90). Both (*)NO elevations and the association between nNOS and Hsp90 were inhibited in rats infused with superoxide dismutase. Elevations of (*)NO were also inhibited by treatment with the relatively specific nNOS inhibitor, 7 nitroindazole, by the ansamycin antibiotics herbimycin and geldanamycin, by the antioxidant N-acetylcysteine, by the calcium channel blocker nimodipine, and by the N-methyl-D-aspartate inhibitor, MK 801. Hyperoxia did not alter eNOS association with Hsp90, nor did it modify nNOS or eNOS associations with calmodulin, the magnitude of eNOS tyrosine phosphorylation, or nNOS phosphorylation via calmodulin kinase. Cerebral cortex blood flow, measured by laser Doppler flow probe, increased during hyperoxia and may be causally related to elevations of steady state (*)NO concentration. We conclude that hyperoxia causes an increase in (*)NO synthesis as part of a response to oxidative stress. Mechanisms for nNOS activation include augmentation in the association with Hsp90 and intracellular entry of calcium.
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Details
- Title
- Stimulation of nitric oxide synthase in cerebral cortex due to elevated partial pressures of oxygen: an oxidative stress response
- Creators
- Stephen R Thom - University of PennsylvaniaVeena Bhopale - University of PennsylvaniaDonald Fisher - University of PennsylvaniaYefim Manevich - University of PennsylvaniaPaul L Huang - Massachusetts General HospitalDonald G Buerk - University of Pennsylvania
- Publication Details
- Journal of neurobiology, v 51(2), pp 85-100
- Publisher
- Wiley
- Grant note
- ES-05211 / NIEHS NIH HHS NS-33335 / NINDS NIH HHS AT-00428 / NCCIH NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000175020300001
- Scopus ID
- 2-s2.0-0036216963
- Other Identifier
- 991019231736904721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences