"Oxygen sensing" by Na,K-ATPase: These miraculous thiols

Control over the Na,K-ATPase function plays a central role in adaptation of the organisms to hypoxic and anoxic conditions. As the enzyme itself does not possess O2 binding sites its "oxygen-sensitivity" is mediated by a variety of redox-sensitive modifications including S-glutathionylatio...

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Authors: Bogdanova, Anna, Petrushanko, Irina Y., Hernansanz Agustín, Pablo
Format: article
Publication Date:2016
Country:España
Institution:Universidad Autónoma de Madrid
Repository:Biblos-e Archivo. Repositorio Institucional de la UAM
Language:English
OAI Identifier:oai:repositorio.uam.es:10486/678039
Online Access:http://hdl.handle.net/10486/678039
https://dx.doi.org/10.3389/fphys.2016.00314
Access Level:Open access
Keyword:Hypoxia
Redox regulation
S-glutathionylation
S-nitrosylation
Sodium-Potassium-Exchanging ATPase
Thiols
Medicina
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spelling "Oxygen sensing" by Na,K-ATPase: These miraculous thiolsBogdanova, AnnaPetrushanko, Irina Y.Hernansanz Agustín, PabloHypoxiaRedox regulationS-glutathionylationS-nitrosylationSodium-Potassium-Exchanging ATPaseThiolsMedicinaControl over the Na,K-ATPase function plays a central role in adaptation of the organisms to hypoxic and anoxic conditions. As the enzyme itself does not possess O2 binding sites its "oxygen-sensitivity" is mediated by a variety of redox-sensitive modifications including S-glutathionylation, S-nitrosylation, and redox-sensitive phosphorylation. This is an overview of the current knowledge on the plethora of molecular mechanisms tuning the activity of the ATP-consuming Na,K-ATPase to the cellular metabolic activity. Recent findings suggest that oxygen-derived free radicals and H2O2, NO, and oxidized glutathione are the signaling messengers that make the Na,K-ATPase "oxygen-sensitive." This very ancient signaling pathway targeting thiols of all three subunits of the Na,K-ATPase as well as redox-sensitive kinases sustains the enzyme activity at the "optimal" level avoiding terminal ATP depletion and maintaining the transmembrane ion gradients in cells of anoxia-tolerant species. We acknowledge the complexity of the underlying processes as we characterize the sources of reactive oxygen and nitrogen species production in hypoxic cells, and identify their targets, the reactive thiol groups which, upon modification, impact the enzyme activity. Structured accordingly, this review presents a summary on (i) the sources of free radical production in hypoxic cells, (ii) localization of regulatory thiols within the Na,K-ATPase and the role reversible thiol modifications play in responses of the enzyme to a variety of stimuli (hypoxia, receptors' activation) (iii) redox-sensitive regulatory phosphorylation, and (iv) the role of fine modulation of the Na,K-ATPase function in survival success under hypoxic conditions. The co-authors attempted to cover all the contradictions and standing hypotheses in the field and propose the possible future developments in this dynamic area of research, the importance of which is hard to overestimate. Better understanding of the processes underlying successful adaptation strategies will make it possible to harness them and use for treatment of patients with stroke and myocardial infarction, sleep apnoea and high altitude pulmonary oedema, and those undergoing surgical interventions associated with the interruption of blood perfusion.The review was funded by the grants of Swiss Nationa lScience Foundation IZK0Z3_157269/1 and 310030_124970/1 to AB and Russian Science Foundation (Grant#14-14-01152) to IP Spanish Government grants (partially funded by the European Union FEDER/EDRF) PI12/00875 and PI15/00107 and a grant from the Fundación Domingo Martínez are supporting AM, PH received a travel grant from the Instituto de Investigación Sanitaria Princesa (to PH),and by COST actions TD0901 (HypoxiaNet) and CM1001. PH is recipient of a pre-doctoral FPU fellowship from the Spanish Government and AM is supported by the I3SNS programme (ISCIII, Spanish Government, partially funded by FEDER/ERDF)Frontiers Research FoundationDepartamento de BioquímicaFacultad de MedicinaInstituto de Investigación del Hospital de La Princesa (IP)20162016-08-02research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/678039https://dx.doi.org/10.3389/fphys.2016.00314reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6780392026-06-23T12:46:27Z
dc.title.none.fl_str_mv "Oxygen sensing" by Na,K-ATPase: These miraculous thiols
title "Oxygen sensing" by Na,K-ATPase: These miraculous thiols
spellingShingle "Oxygen sensing" by Na,K-ATPase: These miraculous thiols
Bogdanova, Anna
Hypoxia
Redox regulation
S-glutathionylation
S-nitrosylation
Sodium-Potassium-Exchanging ATPase
Thiols
Medicina
title_short "Oxygen sensing" by Na,K-ATPase: These miraculous thiols
title_full "Oxygen sensing" by Na,K-ATPase: These miraculous thiols
title_fullStr "Oxygen sensing" by Na,K-ATPase: These miraculous thiols
title_full_unstemmed "Oxygen sensing" by Na,K-ATPase: These miraculous thiols
title_sort "Oxygen sensing" by Na,K-ATPase: These miraculous thiols
dc.creator.none.fl_str_mv Bogdanova, Anna
Petrushanko, Irina Y.
Hernansanz Agustín, Pablo
author Bogdanova, Anna
author_facet Bogdanova, Anna
Petrushanko, Irina Y.
Hernansanz Agustín, Pablo
author_role author
author2 Petrushanko, Irina Y.
Hernansanz Agustín, Pablo
author2_role author
author
dc.contributor.none.fl_str_mv Departamento de Bioquímica
Facultad de Medicina
Instituto de Investigación del Hospital de La Princesa (IP)
dc.subject.none.fl_str_mv Hypoxia
Redox regulation
S-glutathionylation
S-nitrosylation
Sodium-Potassium-Exchanging ATPase
Thiols
Medicina
topic Hypoxia
Redox regulation
S-glutathionylation
S-nitrosylation
Sodium-Potassium-Exchanging ATPase
Thiols
Medicina
description Control over the Na,K-ATPase function plays a central role in adaptation of the organisms to hypoxic and anoxic conditions. As the enzyme itself does not possess O2 binding sites its "oxygen-sensitivity" is mediated by a variety of redox-sensitive modifications including S-glutathionylation, S-nitrosylation, and redox-sensitive phosphorylation. This is an overview of the current knowledge on the plethora of molecular mechanisms tuning the activity of the ATP-consuming Na,K-ATPase to the cellular metabolic activity. Recent findings suggest that oxygen-derived free radicals and H2O2, NO, and oxidized glutathione are the signaling messengers that make the Na,K-ATPase "oxygen-sensitive." This very ancient signaling pathway targeting thiols of all three subunits of the Na,K-ATPase as well as redox-sensitive kinases sustains the enzyme activity at the "optimal" level avoiding terminal ATP depletion and maintaining the transmembrane ion gradients in cells of anoxia-tolerant species. We acknowledge the complexity of the underlying processes as we characterize the sources of reactive oxygen and nitrogen species production in hypoxic cells, and identify their targets, the reactive thiol groups which, upon modification, impact the enzyme activity. Structured accordingly, this review presents a summary on (i) the sources of free radical production in hypoxic cells, (ii) localization of regulatory thiols within the Na,K-ATPase and the role reversible thiol modifications play in responses of the enzyme to a variety of stimuli (hypoxia, receptors' activation) (iii) redox-sensitive regulatory phosphorylation, and (iv) the role of fine modulation of the Na,K-ATPase function in survival success under hypoxic conditions. The co-authors attempted to cover all the contradictions and standing hypotheses in the field and propose the possible future developments in this dynamic area of research, the importance of which is hard to overestimate. Better understanding of the processes underlying successful adaptation strategies will make it possible to harness them and use for treatment of patients with stroke and myocardial infarction, sleep apnoea and high altitude pulmonary oedema, and those undergoing surgical interventions associated with the interruption of blood perfusion.
publishDate 2016
dc.date.none.fl_str_mv 2016
2016-08-02
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/678039
https://dx.doi.org/10.3389/fphys.2016.00314
url http://hdl.handle.net/10486/678039
https://dx.doi.org/10.3389/fphys.2016.00314
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Research Foundation
publisher.none.fl_str_mv Frontiers Research Foundation
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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