Oxidative stress in the systemic and cellular responses to intermittent hypoxia
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N. R. Prabhakar
Abstract
Patients with chronic intermittent hypoxia (IH) caused by recurrent apneas have a greatly increased risk for developing hypertension, myocardial infarctions, and stroke. The purpose of this article is to highlight some of the recent studies focusing on the mechanisms associated with systemic and cellular effects of IH in experimental animals and cell culture models. Rats exposed to chronic IH exhibited elevated blood pressures and increased sympathetic nerve activity, partly due to enhanced reflexes arising from carotid bodies. Direct recordings of the carotid body sensory activity showed that chronic IH selectively augmented hypoxic sensitivity, and induced a novel form of functional plasticity manifested as sensory longterm facilitation. In cell culture models, prior exposure to IH resulted in facilitation of hypoxiainduced transmitter release and activation of several protein kinases. IH caused activation of cFos and activator protein-1 (AP-1) transcription factor and tyrosine hydroxylase, an APregulated downstream gene. For a given duration and intensity of hypoxia, IH was more potent and caused longerlasting activation than continuous hypoxia. Scavengers of reactive oxygen species (ROS) prevented IHinduced systemic and cellular responses. Inhibition of complex I of the mitochondrial electron transport chain appears to be one of the sources for IHinduced generation of ROS. The persistent oxidative stress may contribute to the progression of morbidity associated with chronic IH caused by recurrent apneas, and antioxidants might be of considerable therapeutic value in preventing the progression of disease associated with chronic IH.
Copyright © 2004 by Walter de Gruyter GmbH & Co. KG
Articles in the same Issue
- Oxygen and the Cell
- O2 sensing in the human ductus arteriosus: redox-sensitive K+ channels are regulated by mitochondria-derived hydrogen peroxide
- Oxidative stress in the systemic and cellular responses to intermittent hypoxia
- HIF hydroxylation and cellular oxygen sensing
- Visualization of the three-dimensional organization of hypoxia-inducible factor-1α and interacting cofactors in subnuclear structures
- Modulation of glucokinase expression by hypoxia-inducible factor 1 and upstream stimulatory factor 2 in primary rat hepatocytes
- Redox-sensitive regulation of the HIF pathway under non-hypoxic conditions in pulmonary artery smooth muscle cells
- Measurement of exhaled hydrogen peroxide from rabbit lungs
- Effects of reducing agents on glutathione metabolism and the function of carotid body chemoreceptor cells
- Expression of functional purinergic receptors in pulmonary neuroepithelial bodies and their role in hypoxia chemotransmission
- Remodelling of Ca2+ homeostasis in type I cortical astrocytes by hypoxia: evidence for association with Alzheimer's disease
- Simultaneous exposure of rats to dioxin and carbon monoxide reduces the xenobiotic but not the hypoxic response
- Structure and expression of two kininogen genes in mice
- The central domain of the matrix protein of HIV-1: influence on protein structure and virus infectivity
- Skin secretion of the toad Bombina variegata contains multiple insulin-releasing peptides including bombesin and entirely novel insulinotropic structures
- Inhibition of lentil copper/TPQ amine oxidase by the mechanism-based inhibitor derived from tyramine
- Enhanced expression of basolateral multidrug resistance protein isoforms Mrp3 and Mrp5 in rat liver by LPS
- Critical O2 and NO concentrations in NO-induced cell death in a rat liver sinusoidal endothelial cell line
Articles in the same Issue
- Oxygen and the Cell
- O2 sensing in the human ductus arteriosus: redox-sensitive K+ channels are regulated by mitochondria-derived hydrogen peroxide
- Oxidative stress in the systemic and cellular responses to intermittent hypoxia
- HIF hydroxylation and cellular oxygen sensing
- Visualization of the three-dimensional organization of hypoxia-inducible factor-1α and interacting cofactors in subnuclear structures
- Modulation of glucokinase expression by hypoxia-inducible factor 1 and upstream stimulatory factor 2 in primary rat hepatocytes
- Redox-sensitive regulation of the HIF pathway under non-hypoxic conditions in pulmonary artery smooth muscle cells
- Measurement of exhaled hydrogen peroxide from rabbit lungs
- Effects of reducing agents on glutathione metabolism and the function of carotid body chemoreceptor cells
- Expression of functional purinergic receptors in pulmonary neuroepithelial bodies and their role in hypoxia chemotransmission
- Remodelling of Ca2+ homeostasis in type I cortical astrocytes by hypoxia: evidence for association with Alzheimer's disease
- Simultaneous exposure of rats to dioxin and carbon monoxide reduces the xenobiotic but not the hypoxic response
- Structure and expression of two kininogen genes in mice
- The central domain of the matrix protein of HIV-1: influence on protein structure and virus infectivity
- Skin secretion of the toad Bombina variegata contains multiple insulin-releasing peptides including bombesin and entirely novel insulinotropic structures
- Inhibition of lentil copper/TPQ amine oxidase by the mechanism-based inhibitor derived from tyramine
- Enhanced expression of basolateral multidrug resistance protein isoforms Mrp3 and Mrp5 in rat liver by LPS
- Critical O2 and NO concentrations in NO-induced cell death in a rat liver sinusoidal endothelial cell line
