Acute hypercapnic hyperoxia stimulates reactive species production in the caudal solitary complex of rat brain slices but does not induce oxidative stress
Abstract
Central CO2chemoreceptive neurons in the caudal solitary complex (cSC) are stimulated by hyperoxia via a free radical mechanism. Hyperoxia has been shown to increase superoxide and nitric oxide in the cSC, but it remains unknown how changes in Pco2during hyperoxia affect the production of O2-dependent reactive oxygen and nitrogen species (RONS) downstream that can lead to increased levels of oxidative and nitrosative stress, cellular excitability, and, potentially, dysfunction. We used real-time fluorescence microscopy in rat brain slices to determine how hyperoxia and hypercapnic acidosis (HA) modulate one another in the production of key RONS, as well as colorimetric assays to measure levels of oxidized and nitrated lipids and proteins. We also examined the effects of CO2narcosis and hypoxia before euthanasia and brain slice harvesting, as these neurons are CO2sensitive and hypothesized to employ CO2/H+mechanisms that exacerbate RONS production and potentially oxidative stress. Our findings show that hyperoxia ± HA increases the production of peroxynitrite and its derivatives, whereas increases in Fenton chemistry are most prominent during hyperoxia + HA. Using CO2narcosis before euthanasia modulates cellular sensitivity to HA postmortem and enhances the magnitude of the peroxynitrite pathway, but blunts the activity of Fenton chemistry. Overall, hyperoxia and HA do not result in increased production of markers of oxidative and nitrosative stress as expected. We postulate this is due to antioxidant and proteosomal removal of damaged lipids and proteins to maintain cell viability and avoid death during protracted hyperoxia.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Dec 01, 2016
- Source ID
- 10.1152/ajpcell.00161.2016
Entities
People
- Geoffrey E. Ciarlone
- Jay B. Dean
Organizations
- Office of Naval Research
- University of South Florida