Journal article

Publication year: 2012

Pages: 1033-1042

Journal: Free Radical Biology and Medicine

Volume number: 52

Issue number: 6

ISSN: 0891-5849

eISSN: 1873-4596

DOI Link: https://doi.org/10.1016/j.freeradbiomed.2011.12.004

Publisher: Elsevier

Abstract: 
There is current discussion whether reactive oxygen species are up- or downregulated in the pulmonary circulation during hypoxia, from which sources (i.e., mitochondria or NADPH oxidases) they are derived, and what the downstream targets of ROS are. We recently showed that the NADPH oxidase homolog NOX4 is upregulated in hypoxia-induced pulmonary hypertension in mice and contributes to the vascular remodeling in pulmonary hypertension. We here tested the hypothesis that NOX4 regulates K-v channels via an increased ROS formation after prolonged hypoxia. We showed that (1) NOX4 is upregulated in hypoxia-induced pulmonary hypertension in rats and isolated rat pulmonary arterial smooth muscle cells (PASMC) after 3 days of hypoxia, and (2) that NOX4 is a major contributor to increased reactive oxygen species (ROS) after hypoxia. Our data indicate colocalization of K-v 1.5 and NOX4 in isolated PASMC. The NADPH oxidase inhibitor and ROS scavenger apocynin as well as NOX4 siRNA reversed the hypoxia-induced decrease in K-v current density whereas the protein levels of the channels remain unaffected by siNOX4 treatment. Determination of cysteine oxidation revealed increased NOX4-mediated K-v 1.5 channel oxidation. We conclude that sustained hypoxia decreases K-v channel currents by a direct effect of a NOX4-derived increase in ROS. (C) 2011 Elsevier Inc. All rights reserved.

Harvard Citation style: Mittal, M., Gu, X., Pak, O., Pamenter, M., Haag, D., Fuchs, D., et al. (2012) Hypoxia induces K_v channel current inhibition by increased NADPH oxidase-derived reactive oxygen species, Free Radical Biology and Medicine, 52(6), pp. 1033-1042. https://doi.org/10.1016/j.freeradbiomed.2011.12.004

APA Citation style: Mittal, M., Gu, X., Pak, O., Pamenter, M., Haag, D., Fuchs, D., Schermuly, R., Ghofrani, H., Brandes, R., Seeger, W., Grimminger, F., Haddad, G., & Weissmann, N. (2012). Hypoxia induces K_v channel current inhibition by increased NADPH oxidase-derived reactive oxygen species. Free Radical Biology and Medicine. 52(6), 1033-1042. https://doi.org/10.1016/j.freeradbiomed.2011.12.004