{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T13:18:14Z","timestamp":1791206294458,"version":"4.1.0"},"reference-count":34,"publisher":"National Academy of Sciences","issue":"19","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,5,7]]},"abstract":"<jats:p>\n                    Breathing and blood pressure are under constant homeostatic regulation to maintain optimal oxygen delivery to the tissues. Chemosensory reflexes initiated by the carotid body and catecholamine secretion from the adrenal medulla are the principal mechanisms for maintaining respiratory and cardiovascular homeostasis; however, the underlying molecular mechanisms are not known. Here, we report that balanced activity of hypoxia-inducible factor-1 (HIF-1) and HIF-2 is critical for oxygen sensing by the carotid body and adrenal medulla, and for their control of cardio-respiratory function. In\n                    <jats:italic>Hif2\u03b1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice, partial HIF-2\u03b1 deficiency increased levels of HIF-1\u03b1 and NADPH oxidase 2, leading to an oxidized intracellular redox state, exaggerated hypoxic sensitivity, and cardio-respiratory abnormalities, which were reversed by treatment with a HIF-1\u03b1 inhibitor or a superoxide anion scavenger. Conversely, in\n                    <jats:italic>Hif1\u03b1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice, partial HIF-1\u03b1 deficiency increased levels of HIF-2\u03b1 and superoxide dismutase 2, leading to a reduced intracellular redox state, blunted oxygen sensing, and impaired carotid body and ventilatory responses to chronic hypoxia, which were corrected by treatment with a HIF-2\u03b1 inhibitor. None of the abnormalities observed in\n                    <jats:italic>Hif1\u03b1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice or\n                    <jats:italic>Hif2\u03b1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice were observed in\n                    <jats:italic>Hif1\u03b1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    ;\n                    <jats:italic>Hif2\u03b1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice. These observations demonstrate that redox balance, which is determined by mutual antagonism between HIF-\u03b1 isoforms, establishes the set point for hypoxic sensing by the carotid body and adrenal medulla, and is required for maintenance of cardio-respiratory homeostasis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1305961110","type":"journal-article","created":{"date-parts":[[2013,4,23]],"date-time":"2013-04-23T03:10:22Z","timestamp":1366686622000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":70,"title":["RETRACTED: Mutual antagonism between hypoxia-inducible factors 1\u03b1 and 2\u03b1 regulates oxygen sensing and cardio-respiratory homeostasis"],"prefix":"10.1073","volume":"110","author":[{"given":"Guoxiang","family":"Yuan","sequence":"first","affiliation":[{"name":"Biological Sciences Division, Institute for Integrative Physiology and Center for Systems Biology of O2 Sensing, University of Chicago, IL 60637;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Jie","family":"Peng","sequence":"additional","affiliation":[{"name":"Biological Sciences Division, Institute for Integrative Physiology and Center for Systems Biology of O2 Sensing, University of Chicago, IL 60637;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaddi Damodara","family":"Reddy","sequence":"additional","affiliation":[{"name":"Biological Sciences Division, Institute for Integrative Physiology and Center for Systems Biology of O2 Sensing, University of Chicago, IL 60637;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladislav V.","family":"Makarenko","sequence":"additional","affiliation":[{"name":"Biological Sciences Division, Institute for Integrative Physiology and Center for Systems Biology of O2 Sensing, University of Chicago, IL 60637;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayasri","family":"Nanduri","sequence":"additional","affiliation":[{"name":"Biological Sciences Division, Institute for Integrative Physiology and Center for Systems Biology of O2 Sensing, University of Chicago, IL 60637;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shakil A.","family":"Khan","sequence":"additional","affiliation":[{"name":"Biological Sciences Division, Institute for Integrative Physiology and Center for Systems Biology of O2 Sensing, University of Chicago, IL 60637;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph A.","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Medicine, Veterans Affairs North Texas Health Care System, Dallas, TX 75216;"},{"name":"Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganesh K.","family":"Kumar","sequence":"additional","affiliation":[{"name":"Biological Sciences Division, Institute for Integrative Physiology and Center for Systems Biology of O2 Sensing, University of Chicago, IL 60637;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregg L.","family":"Semenza","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, Medicine, Oncology, Radiation Oncology, and Biological Chemistry,"},{"name":"Vascular Program, Institute for Cell Engineering, and"},{"name":"McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanduri R.","family":"Prabhakar","sequence":"additional","affiliation":[{"name":"Biological Sciences Division, Institute for Integrative Physiology and Center for Systems Biology of O2 Sensing, University of Chicago, IL 60637;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2013,4,22]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09486"},{"key":"e_1_3_3_2_2","first-page":"273","article-title":"Sur les modifications directes et sur la regulation reflexe de l\u2019activitie du centre respiratoire de la tete isolee du chien","volume":"33","author":"Heymans J","year":"1927","unstructured":"J Heymans, C Heymans, Sur les modifications directes et sur la regulation reflexe de l\u2019activitie du centre respiratoire de la tete isolee du chien. 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