Publication:
Acute oxygen sensing in heme oxygenase-2 null mice.

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Date

2006-10

Authors

Ortega-Sáenz, Patricia
Pascual, Alberto
Gómez-Díaz, Raquel
López-Barneo, José

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Rockefeller University Press
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Abstract

Hemeoxygenase-2 (HO-2) is an antioxidant enzyme that can modulate recombinant maxi-K(+) channels and has been proposed to be the acute O(2) sensor in the carotid body (CB). We have tested the physiological contribution of this enzyme to O(2) sensing using HO-2 null mice. HO-2 deficiency leads to a CB phenotype characterized by organ growth and alteration in the expression of stress-dependent genes, including the maxi-K(+) channel alpha-subunit. However, sensitivity to hypoxia of CB is remarkably similar in HO-2 null animals and their control littermates. Moreover, the response to hypoxia in mouse and rat CB cells was maintained after blockade of maxi-K(+) channels with iberiotoxin. Hypoxia responsiveness of the adrenal medulla (AM) (another acutely responding O(2)-sensitive organ) was also unaltered by HO-2 deficiency. Our data suggest that redox disregulation resulting from HO-2 deficiency affects maxi-K(+) channel gene expression but it does not alter the intrinsic O(2) sensitivity of CB or AM cells. Therefore, HO-2 is not a universally used acute O(2) sensor.

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Journal Article; Research Support, Non-U.S. Gov't;. A Pascual is an investigator of the “Ramón y Cajal” program. J. López-Barneo received the “Ayuda a la Investigación 2000” of the Juan March Foundation

MeSH Terms

Medical Subject Headings::Organisms::Eukaryota::Animals
Medical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Newborn
Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Signs and Symptoms, Respiratory::Anoxia
Medical Subject Headings::Chemicals and Drugs::Inorganic Chemicals::Elements::Metals, Alkaline Earth::Calcium
Medical Subject Headings::Anatomy::Nervous System::Neurons::Neurons, Afferent::Sensory Receptor Cells::Chemoreceptor Cells::Paraganglia, Nonchromaffin::Carotid Body
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amines::Catecholamines
Medical Subject Headings::Anatomy::Cells::Chromaffin Cells
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Isomerases::cis-trans-Isomerases::Peptidylprolyl Isomerase::Immunophilins::Cyclophilins
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Oxidoreductases::Oxygenases::Mixed Function Oxygenases::Heme Oxygenase (Decyclizing)
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Oxidoreductases::Oxygenases::Mixed Function Oxygenases::Heme Oxygenase (Decyclizing)::Heme Oxygenase-1
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Carrier Proteins::Membrane Transport Proteins::Ion Channels::Potassium Channels::Potassium Channels, Calcium-Activated::Large-Conductance Calcium-Activated Potassium Channels
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice
Medical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Inbred Strains::Mice, Inbred Strains::Mice, Inbred C57BL
Medical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Genetically Modified::Mice, Transgenic::Mice, Knockout
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Body Constitution::Body Weights and Measures::Organ Size
Medical Subject Headings::Chemicals and Drugs::Inorganic Chemicals::Elements::Chalcogens::Oxygen
Medical Subject Headings::Phenomena and Processes::Physical Phenomena::Mechanical Phenomena::Pressure::Partial Pressure
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Cytological Techniques::Patch-Clamp Techniques
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Membrane Transport Modulators::Potassium Channel Blockers
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats
Tyrosine 3-Monooxygenase
Medical Subject Headings::Anatomy::Endocrine System::Endocrine Glands::Adrenal Glands::Adrenal Medulla

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Keywords

Animales, Animales Recién Nacidos, Calcio, Cuerpo Carotídeo, Catecolaminas, Células Cromafines, Ciclofilinas, Expresión Génica, Hemo Oxigenasa (Deciclizadora), Hemo-Oxigenasa 1, Subunidades alfa de los Canales de Potasio de Gran Conductancia Activados por Calcio, Canales de Potasio de Gran Conductancia Activados por el Calcio, Ratones, Ratones Consanguíneos C57BL, Ratones Noqueados, Tamaño de los Órganos, Oxígeno, Presión Parcial, Técnicas de Placa-Clamp, Péptidos, Bloqueadores de los Canales de Potasio, Ratas, Médula Suprarrenal

Citation

Ortega-Sáenz P, Pascual A, Gómez-Díaz R, López-Barneo J. Acute oxygen sensing in heme oxygenase-2 null mice. J Gen Physiol. 2006; 128(4):405-1