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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Biosensing Techniques / methods*
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Cell Line
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Cell Membrane / metabolism
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Enzyme Inhibitors / pharmacology
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Humans
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Hypoxia / metabolism
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Hypoxia-Inducible Factor 1, alpha Subunit / drug effects
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
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NADPH Oxidase 4
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NADPH Oxidases / antagonists & inhibitors
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NADPH Oxidases / genetics
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NADPH Oxidases / physiology*
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Nerve Tissue Proteins
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Onium Compounds / pharmacology
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Oxygen / analysis
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Oxygen / metabolism*
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Potassium / metabolism
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Potassium / physiology
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Potassium Channels, Tandem Pore Domain / antagonists & inhibitors
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Potassium Channels, Tandem Pore Domain / metabolism*
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RNA, Small Interfering / genetics
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RNA, Small Interfering / pharmacology
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RNA, Small Interfering / physiology
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Signal Transduction / drug effects
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Signal Transduction / physiology
Substances
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Enzyme Inhibitors
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Hypoxia-Inducible Factor 1, alpha Subunit
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Nerve Tissue Proteins
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Onium Compounds
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Potassium Channels, Tandem Pore Domain
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RNA, Small Interfering
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potassium channel subfamily K member 3
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diphenyleneiodonium
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NADPH Oxidase 4
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NADPH Oxidases
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NOX4 protein, human
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Potassium
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Oxygen