NOX4 as an oxygen sensor to regulate TASK-1 activity

Young Mee Lee, Byung Joo Kim, Yang Sook Chun, Insuk So, Hyunsung Choi, Myung Suk Kim, Jong Wan Park

Research output: Contribution to journalArticle

88 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)499-507
Number of pages9
JournalCellular Signalling
Volume18
Issue number4
DOIs
StatePublished - 1 Apr 2006

Fingerprint

Oxygen
NADPH Oxidase
Cell Hypoxia
HEK293 Cells
Small Interfering RNA
Cell Membrane
Proteins
Hypoxia

Keywords

  • NOX4
  • Oxygen sensing
  • Reactive oxygen species
  • TASK-1

Cite this

Lee, Young Mee ; Kim, Byung Joo ; Chun, Yang Sook ; So, Insuk ; Choi, Hyunsung ; Kim, Myung Suk ; Park, Jong Wan. / NOX4 as an oxygen sensor to regulate TASK-1 activity. In: Cellular Signalling. 2006 ; Vol. 18, No. 4. pp. 499-507.
@article{436fbdfc12bf48588a5bb3977993081b,
title = "NOX4 as an oxygen sensor to regulate TASK-1 activity",
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.",
keywords = "NOX4, Oxygen sensing, Reactive oxygen species, TASK-1",
author = "Lee, {Young Mee} and Kim, {Byung Joo} and Chun, {Yang Sook} and Insuk So and Hyunsung Choi and Kim, {Myung Suk} and Park, {Jong Wan}",
year = "2006",
month = "4",
day = "1",
doi = "10.1016/j.cellsig.2005.05.025",
language = "English",
volume = "18",
pages = "499--507",
journal = "Cellular Signalling",
issn = "0898-6568",
publisher = "Elsevier Inc.",
number = "4",

}

NOX4 as an oxygen sensor to regulate TASK-1 activity. / Lee, Young Mee; Kim, Byung Joo; Chun, Yang Sook; So, Insuk; Choi, Hyunsung; Kim, Myung Suk; Park, Jong Wan.

In: Cellular Signalling, Vol. 18, No. 4, 01.04.2006, p. 499-507.

Research output: Contribution to journalArticle

TY - JOUR

T1 - NOX4 as an oxygen sensor to regulate TASK-1 activity

AU - Lee, Young Mee

AU - Kim, Byung Joo

AU - Chun, Yang Sook

AU - So, Insuk

AU - Choi, Hyunsung

AU - Kim, Myung Suk

AU - Park, Jong Wan

PY - 2006/4/1

Y1 - 2006/4/1

N2 - 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.

AB - 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.

KW - NOX4

KW - Oxygen sensing

KW - Reactive oxygen species

KW - TASK-1

UR - http://www.scopus.com/inward/record.url?scp=29044437140&partnerID=8YFLogxK

U2 - 10.1016/j.cellsig.2005.05.025

DO - 10.1016/j.cellsig.2005.05.025

M3 - Article

C2 - 16019190

AN - SCOPUS:29044437140

VL - 18

SP - 499

EP - 507

JO - Cellular Signalling

JF - Cellular Signalling

SN - 0898-6568

IS - 4

ER -