NOX4 as an oxygen sensor to regulate TASK-1 activity

Lee, Young-Mee; Kim, Byung-Joo; Chun, Yang–Sook; So, Insuk; Choi, Han Sung; Kim, Myung-Suk; Park, Jong-Wan

doi:10.1016/j.cellsig.2005.05.025

Cited by 98 publications

(79 citation statements)

References 26 publications

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“…Thus, while NOX4 may be a normal component of differentiated pulmonary smooth muscle cells, its upregulation by inflammatory stimuli that promote fibrosis, such as TGF-β, suggests an important contribution of NOX4 in fibrotic lung disease. Recent studies suggest that NOX4 may also function as an oxygen sensor, by regulating the O 2 -sensitive K+ channel, TASK-1 (192).…”

Section: Functional Aspects Of Nox In Other Lung Cell Typesmentioning

confidence: 99%

NADPH oxidases in lung biology and pathology: Host defense enzymes, and more

Vliet

2008

Free Radical Biology and Medicine

186

192

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The deliberate production of reactive oxygen species (ROS) by phagocyte NADPH oxidase is widely appreciated as a critical component of antimicrobial host defense. Recently, additional homologs of NADPH oxidase (NOX) have been discovered throughout the animal and plant kingdoms, which appear to possess diverse functions in addition to host defense, including cell proliferation, differentiation, and regulation of gene expression. Several of these NOX homologs are also expressed within the respiratory tract, where they participate in innate host defense as well as in epithelial and inflammatory cell signaling and gene expression, and fibroblast and smooth muscle cell proliferation, in response to bacterial or viral infection and environmental stress. Inappropriate expression or activation of NOX/DUOX during various lung pathologies suggests their specific involvement in respiratory disease. This review summarizes the current state of knowledge regarding the general functional properties of mammalian NOX enzymes, and their specific importance in respiratory tract physiology and pathology.

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Section: Functional Aspects Of Nox In Other Lung Cell Typesmentioning

confidence: 99%

NADPH oxidases in lung biology and pathology: Host defense enzymes, and more

Vliet

2008

Free Radical Biology and Medicine

186

192

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“…However, there is evidence suggesting that NOX4, not NOX2, is the primary isoform in chemoreceptors (75). Expression of TASK-1 channels in human embryonic kidney (HEK) cells revealed not only that these currents were inhibited by hypoxia but also that NOX4 colocalized with TASK-1, and that depletion of endogenous NOX4 abolished the O 2 sensitivity of the current (122). Whether this also occurs in chemoreceptors, or whether other NOX isoforms might be involved, is unknown.…”

Section: Chemoreceptorsmentioning

confidence: 99%

Hypoxia. 4. Hypoxia and ion channel function

Shimoda

Polàk

2011

American Journal of Physiology-Cell Physiology

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The ability to sense and respond to oxygen deprivation is required for survival; thus, understanding the mechanisms by which changes in oxygen are linked to cell viability and function is of great importance. Ion channels play a critical role in regulating cell function in a wide variety of biological processes, including neuronal transmission, control of ventilation, cardiac contractility, and control of vasomotor tone. Since the 1988 discovery of oxygen-sensitive potassium channels in chemoreceptors, the effect of hypoxia on an assortment of ion channels has been studied in an array of cell types. In this review, we describe the effects of both acute and sustained hypoxia (continuous and intermittent) on mammalian ion channels in several tissues, the mode of action, and their contribution to diverse cellular processes. oxygen deprivation; mammalian ion channels; oxygen homeostasis SENSING and appropriately responding to changes in O 2 concentration is of paramount importance for the survival of all organisms. Over time, O 2 homeostasis has evolved into a complex system to regulate O 2 delivery and use. While the rapid response to acute reductions in O 2 concentration typically results from processes that alter preexisting proteins, such as phosphorylation, stabilization, dimerization, or degradation, durable adaptation to prolonged hypoxic insult requires a coordinated response at the level of gene transcription. Since a deficit in O 2 is an important component of various physiological processes and the pathogenesis of numerous diseases, understanding the mechanisms by which changes in O 2 are linked to cell function is of great interest.Ion channels play a critical role in regulating a wide variety of biological processes, including neuronal transmission; control of ventillation; contraction of cardiac, skeletal, and smooth muscle; transport of nutrients and ions across the epithelium; T-cell activation; and glucose metabolism and pancreatic ␤-cell insulin release. To date, over 300 types of ion channels, differing in their mode of activation (voltage-dependent or -independent, ligand-gated, mechanosensitive, pH) and their ionic permeability (K ϩ , Ca 2ϩ , Cl Ϫ , Na ϩ ), have been identified. This heterogeneity in ion channel populations provides an astonishing array of variable responses within and between cell types. In 1988, a report demonstrating that rabbit carotid body glomus cells express an O 2 -sensitive potassium channel ushered in a new era of research exploring whether ion channel activity could be regulated in response to changes in O 2 availability (131). Since that initial description of an O 2 -regulated ion channel, an abundance of work has been produced indicating that a variety of ion channels spread across the different ion channel families are O 2 sensitive and exhibit changes in channel activity with acute hypoxia and alterations in channel quantity with prolonged hypoxic challenge. Although a great amount of work has been devoted to the study of hypoxia and ion channels in reptiles, amp...

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“…Also, the TASK-like current in adrenomedullary chromaffin cell was O 2 insensitive (18). Such results suggested that the O 2 -dependent regulation of TASK is an indirect mechanism signaled from a separate O 2 sensor such as NADPH oxidase (NOX) as has been demonstrated recently (21).…”

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confidence: 48%

Identification of subdomains in NADPH oxidase-4 critical for the oxygen-dependent regulation of TASK-1 K⁺ channels

Park

Chun

Park

et al. 2009

American Journal of Physiology-Cell Physiology

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ϩ current is a critical O2-sensing mechanism. Previously, it was demonstrated that the cooperative action of TASK-1 and NADPH oxidase-4 (NOX4) mediated the O2-sensitive K ϩ current response. Here we addressed the O2-sensing mechanism of NOX4 in terms of TASK-1 regulation. In TASK-1 and NOX4-coexpressing human embryonic kidney 293 cells, hypoxia (5% O2) decreased the amplitude of TASK-1 current (hypoxia-⌬I TASK-1). To examine whether reactive oxygen species (ROS) mediate the hypoxia-⌬ITASK-1, we treated the cells with carbon monoxide (CO) which is known to reduce ROS generation from the heme-containing NOX4. Unexpectedly, CO failed to mimic hypoxia in TASK-1 regulation, rather blocked the hypoxia-⌬ITASK-1. Moreover, the hypoxia-⌬ITASK-1 was neither recovered by H2O2 treatment nor prevented by antioxidant such as ascorbic acid. However, the hypoxia-⌬ITASK-1 was noticeably attenuated by succinyl acetone, a heme synthase inhibitor. To further evaluate the role of heme, we constructed and expressed various NOX4 mutants, such as HBD(Ϫ) lacking the heme binding domain, NBD(Ϫ) lacking the NADPH binding domain, FBD(Ϫ) lacking the FAD binding domain, and HFBD(Ϫ) lacking both heme and FAD domains. The hypoxia-⌬ITASK-1 was significantly reduced in HBD(Ϫ)-, FBD(Ϫ)-, or HFBD(Ϫ)-expressing cells, versus wild-type NOX4-expressing cells. However, NBD(Ϫ) did not affect the TASK-1 response to hypoxia. We also found that p22 is required for the NOX4-dependent TASK-1 regulation. These results suggest that O2 binding with NOX4 per se controls TASK-1 activity. In this process, the heme moiety and FBD seem to be responsible for the NOX4 regulation of TASK-1, and p22 might support the NOX4-TASK-1 interaction. ϩ channel family (K2P). Most of the K2P commonly show background activity that is represented as an ohmic current-to-voltage relation (I-V curve). Such property renders K2P as a primary player setting the hyperpolarized resting membrane potential (5). In contrast with K2P, significant activation of Kv requires membrane depolarization above a threshold. In this respect, the O 2 -sensitivity of TASK is an attractive explanation for the hypoxia-induced initial depolarization of carotid body, neuroepithelial body, cerebellar granule neurons, and pulmonary arterial smooth muscle (3,5,12,13,30).Although the O 2 sensitivity of TASK-like current has been demonstrated in various tissues mentioned above, the responses of heterologously expressed TASK showed somewhat controversial results depending on the expression system. The TASK-1 channels expressed in human embryonic kidney 293 (HEK293) cells showed decreased outward current by hypoxia while those expressed in Xenopus oocytes were insensitive to O 2 (28). Also, the TASK-like current in adrenomedullary chromaffin cell was O 2 insensitive (18). Such results suggested that the O 2 -dependent regulation of TASK is an indirect mechanism signaled from a separate O 2 sensor such as NADPH oxidase (NOX) as has been demonstrated recently (21).NOXs are heme-containing transmembrane proteins to gene...

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NOX4 as an oxygen sensor to regulate TASK-1 activity

Cited by 98 publications

References 26 publications

NADPH oxidases in lung biology and pathology: Host defense enzymes, and more

NADPH oxidases in lung biology and pathology: Host defense enzymes, and more

Hypoxia. 4. Hypoxia and ion channel function

Identification of subdomains in NADPH oxidase-4 critical for the oxygen-dependent regulation of TASK-1 K⁺ channels

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NOX4 as an oxygen sensor to regulate TASK-1 activity

Cited by 98 publications

References 26 publications

NADPH oxidases in lung biology and pathology: Host defense enzymes, and more

NADPH oxidases in lung biology and pathology: Host defense enzymes, and more

Hypoxia. 4. Hypoxia and ion channel function

Identification of subdomains in NADPH oxidase-4 critical for the oxygen-dependent regulation of TASK-1 K+ channels

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Identification of subdomains in NADPH oxidase-4 critical for the oxygen-dependent regulation of TASK-1 K⁺ channels