NOX4 as an oxygen sensor to regulate TASK-1 activity.
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.
Lee
Young-Mee
YM
Department of Physiology and Biophysics, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-799, South Korea.
Kim
Byung-Joo
BJ
Chun
Yang-Sook
YS
So
Insuk
I
Choi
Hyunsung
H
Kim
Myung-Suk
MS
Park
Jong-Wan
JW
D015374:Biosensing Techniques / Q000379:methods*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000187:drug effects / Q000378:metabolism; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D009419:Nerve Tissue Proteins; D009861:Onium Compounds / Q000494:pharmacology; D010100:Oxygen / Q000032:analysis / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism / Q000502:physiology; D024683:Potassium Channels, Tandem Pore Domain / Q000037:antagonists & inhibitors / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009419:Nerve Tissue Proteins; D009861:Onium Compounds; D024683:Potassium Channels, Tandem Pore Domain; D034741:RNA, Small Interfering; C420132:potassium channel subfamily K member 3; C007517:diphenyleneiodonium; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human; D011188:Potassium; D010100:Oxygen