NOX4 as an oxygen sensor to regulate TASK-1 activity - PubMed (original) (raw)

Comparative Study

. 2006 Apr;18(4):499-507.

doi: 10.1016/j.cellsig.2005.05.025. Epub 2005 Jul 14.

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Comparative Study

NOX4 as an oxygen sensor to regulate TASK-1 activity

Young-Mee Lee et al. Cell Signal. 2006 Apr.

Abstract

When oxygen sensing cells are excited by hypoxia, background K+ currents are inhibited. TASK-1, which is commonly expressed in oxygen sensing cells and makes a background K+ current, is inactivated by hypoxia. Thus TASK-1 is a candidate molecule responsible for hypoxic excitation. However, TASK-1 per se cannot sense oxygen and may require a regulatory protein that can. In the present study, we propose that the NADPH oxidase NOX4 functions as an oxygen-sensing partner and that it modulates the oxygen sensitivity of TASK-1. Confocal imaging revealed the co-localization of TASK-1 and NOX4 in the plasma membrane. In HEK293 cells expressing NOX4 endogenously, the activity of expressed TASK-1 was moderately inhibited by hypoxia, and this oxygen response was significantly augmented by NOX4. Moreover, the oxygen sensitivity of TASK-1 was abolished by NOX4 siRNA and NADPH oxidase inhibitors. These results suggest a novel function for NOX4 in the oxygen-dependent regulation of TASK-1 activity.

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