caa a22 4500 378919970 CHVBK 20180305123602.0 cr unu---uuuuu 161128e20040413xx s 000 0 eng 10.1515/BC.2004.019 doi (NATIONALLICENCE)gruyter-10.1515/BC.2004.019 Redox-sensitive regulation of the HIF pathway under non-hypoxic conditions in pulmonary artery smooth muscle cells [Elektronische Daten] [R. S. BelAiba, T. Djordjevic, S. Bonello, D. Flügel, J. Hess, T. Kietzmann, A. Görlach] 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 Biochemistry nationallicence Molecular biology nationallicence Cellular biology nationallicence BelAiba R. S. aut Djordjevic T. aut Bonello S. aut Flügel D. aut Hess J. aut Kietzmann T. aut Görlach A. aut Biological Chemistry Walter de Gruyter 385/3-4(2004-04-13), 249-257 1431-6730 385:3-4<249 2004 385 bchm https://doi.org/10.1515/BC.2004.019 text/html Onlinezugriff via DOI 1 research article jats NATIONALLICENCE 856 40 https://doi.org/10.1515/BC.2004.019 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- BelAiba R. S. aut NATIONALLICENCE 700 1- Djordjevic T. aut NATIONALLICENCE 700 1- Bonello S. aut NATIONALLICENCE 700 1- Flügel D. aut NATIONALLICENCE 700 1- Hess J. aut NATIONALLICENCE 700 1- Kietzmann T. aut NATIONALLICENCE 700 1- Görlach A. aut NATIONALLICENCE 773 0- Biological Chemistry Walter de Gruyter 385/3-4(2004-04-13), 249-257 1431-6730 385:3-4<249 2004 385 bchm CC0 http://creativecommons.org/publicdomain/zero/1.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-gruyter