title: Acute hypoxia produces a superoxide burst in cells.
abstract: Oxygen is a key molecule for cell metabolism. Eukaryotic cells sense the reduction in oxygen availability (hypoxia) and trigger a series of cellular and systemic responses to adapt to hypoxia, including the optimization of oxygen consumption. Many of these responses are mediated by a genetic program induced by the hypoxia-inducible transcription factors (HIFs), regulated by a family of prolyl hydroxylases (PHD or EGLN) that use oxygen as a substrate producing HIF hydroxylation. In parallel to these oxygen sensors modulating gene expression within hours, acute modulation of protein function in response to hypoxia is known to occur within minutes. Free radicals acting as second messengers, and oxidative posttranslational modifications, have been implied in both groups of responses. Localization and speciation of the paradoxical increase in reactive oxygen species production in hypoxia remain debatable. We have observed that several cell types respond to acute hypoxia with a transient increase in superoxide production for about 10 min, probably originating in the mitochondria. This may explain in part the apparently divergent results found by various groups that have not taken into account the time frame of hypoxic ROS production. We propose that this acute and transient hypoxia-induced superoxide burst may be translated into oxidative signals contributing to hypoxic adaptation and preconditioning.
authors.affiliation: Servicio de Inmunología, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, E-28006 Madrid, Spain; Departamento de Bioquímica, Facultad de Medicina, Universidad Autónoma de Madrid and Instituto de Investigaciones Biomédicas Alberto Sols, E-28029 Madrid, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Hernansanz-Agustín
authors.affiliation: Servicio de Inmunología, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, E-28006 Madrid, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Izquierdo-Álvarez
authors.affiliation: Laboratorio Mixto, Consejo Superior de Investigaciones Científicas/Fundación Renal "Iñigo Alvarez de Toledo," E-28049 Madrid, Spain; Departamento de Biología Celular e Inmunología, Centro de Biología Molecular "Severo Ochoa," Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, E-28049 Madrid, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Sánchez-Gómez
authors.affiliation: Servicio de Inmunología, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, E-28006 Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Ramos
authors.affiliation: Servicio de Inmunología, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, E-28006 Madrid, Spain.
authors.forename: Tamara
authors.initials: T
authors.lastname: Villa-Piña
authors.affiliation: Laboratorio Mixto, Consejo Superior de Investigaciones Científicas/Fundación Renal "Iñigo Alvarez de Toledo," E-28049 Madrid, Spain; Departamento de Biología Celular e Inmunología, Centro de Biología Molecular "Severo Ochoa," Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, E-28049 Madrid, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Lamas
authors.affiliation: Institute of Veterinary Physiology, Vetsuisse Faculty, and Zurich Center for Integrative Human Physiology, University of Zurich, CH-8057 Zurich, Switzerland.
authors.forename: Anna
authors.initials: A
authors.lastname: Bogdanova
authors.affiliation: Servicio de Inmunología, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, E-28006 Madrid, Spain. Electronic address: amartinezruiz@salud.madrid.org.
authors.forename: Antonio
authors.initials: A
authors.lastname: Martínez-Ruiz
mesh_terms: D000818:Animals; D002417:Cattle; D015687:Cell Hypoxia; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D006900:Hydroxylation; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D010100:Oxygen / Q000494:pharmacology*; D010101:Oxygen Consumption; D016897:Respiratory Burst; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors
chemical_list: D013481:Superoxides; D010100:Oxygen
keywords: Cell signaling; Free radicals; Hypoxia; Ischemia; Oxidative phosphorylation; Reactive oxygen species; Superoxide