Redox-sensitive regulation of the HIF pathway under non-hypoxic conditions in pulmonary artery smooth muscle cells
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R. S. BelAiba
Abstract
Pulmonary hypertension and vascular remodeling processes are associated with oxidative stress, hypoxia and enhanced levels of thrombin and vascular endothelial growth factor (VEGF). The hypoxia-inducible transcription factor HIF regulates the expression of VEGF under hypoxia. The HIF pathway is also activated by thrombin or CoCl2, likely via reactive oxygen species (ROS). In this study we investigated whether the redox-modifying enzymes superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase affect HIF levels and the expression of VEGF mRNA in pulmonary artery smooth muscle cells (PASMC). Stimulation of PASMC with thrombin or CoCl2 increased ROS production and enhanced HIFα protein and VEGF mRNA levels as well as HIFdependent reporter gene activity. These responses were inhibited by vitamin C and by overexpression of GPX and catalase, whereas the opposite effects were observed in SOD-expressing cells. These findings suggest that an antioxidant state with reduced levels of H2O2 limits the activation of the HIF pathway, whereas a prooxidant state allowing elevated H2O2 levels promotes it. Thus, shifting the redox balance to a more reduced environment, thereby limiting VEGF expression, may be beneficial for treating remodeling processes during pulmonary hypertension.
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