{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:29:55Z","timestamp":1791196195084,"version":"4.1.0"},"reference-count":33,"publisher":"National Academy of Sciences","issue":"7","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,2,15]]},"abstract":"<jats:p>\n                    Cardiorespiratory functions in mammals are exquisitely sensitive to changes in arterial O\n                    <jats:sub>2<\/jats:sub>\n                    levels. Hypoxia-inducible factors (e.g., HIF-1 and HIF-2) mediate transcriptional responses to reduced oxygen availability. We demonstrate that haploinsufficiency for the O\n                    <jats:sub>2<\/jats:sub>\n                    -regulated HIF-2\u03b1 subunit results in augmented carotid body sensitivity to hypoxia, irregular breathing, apneas, hypertension, and elevated plasma norepinephrine levels in adult\n                    <jats:italic>\n                      Hif-2\u03b1\n                      <jats:sup>+\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice. These dysregulated autonomic responses were associated with increased oxidative stress and decreased mitochondrial electron transport chain complex I activity in adrenal medullae as a result of decreased expression of major cytosolic and mitochondrial antioxidant enzymes. Systemic administration of a membrane-permeable antioxidant prevented oxidative stress, normalized hypoxic sensitivity of the carotid body, and restored autonomic functions in\n                    <jats:italic>\n                      Hif-2\u03b1\n                      <jats:sup>+\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice. Thus, HIF-2\u03b1\u2013dependent redox regulation is required for maintenance of carotid body function and cardiorespiratory homeostasis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1100064108","type":"journal-article","created":{"date-parts":[[2011,1,31]],"date-time":"2011-01-31T23:07:07Z","timestamp":1296515227000},"page":"3065-3070","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":115,"title":["Hypoxia-inducible factor 2\u03b1 (HIF-2\u03b1) heterozygous-null mice exhibit exaggerated carotid body sensitivity to hypoxia, breathing instability, and hypertension"],"prefix":"10.1073","volume":"108","author":[{"given":"Ying-Jie","family":"Peng","sequence":"first","affiliation":[{"name":"Biological Sciences Division, Institute for Integrated Physiology and Center for Systems Biology of O2 Sensing, University of Chicago, Chicago, IL 60637;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayasri","family":"Nanduri","sequence":"additional","affiliation":[{"name":"Biological Sciences Division, Institute for Integrated Physiology and Center for Systems Biology of O2 Sensing, University of Chicago, Chicago, IL 60637;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shakil A.","family":"Khan","sequence":"additional","affiliation":[{"name":"Biological Sciences Division, Institute for Integrated Physiology and Center for Systems Biology of O2 Sensing, University of Chicago, Chicago, IL 60637;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoxiang","family":"Yuan","sequence":"additional","affiliation":[{"name":"Biological Sciences Division, Institute for Integrated Physiology and Center for Systems Biology of O2 Sensing, University of Chicago, Chicago, IL 60637;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Wang","sequence":"additional","affiliation":[{"name":"Biological Sciences Division, Institute for Integrated Physiology and Center for Systems Biology of O2 Sensing, University of Chicago, Chicago, IL 60637;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Kinsman","sequence":"additional","affiliation":[{"name":"Biological Sciences Division, Institute for Integrated Physiology and Center for Systems Biology of O2 Sensing, University of Chicago, Chicago, IL 60637;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damodara R.","family":"Vaddi","sequence":"additional","affiliation":[{"name":"Biological Sciences Division, Institute for Integrated Physiology and Center for Systems Biology of O2 Sensing, University of Chicago, Chicago, IL 60637;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganesh K.","family":"Kumar","sequence":"additional","affiliation":[{"name":"Biological Sciences Division, Institute for Integrated Physiology and Center for Systems Biology of O2 Sensing, University of Chicago, 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":"Gregg L.","family":"Semenza","sequence":"additional","affiliation":[{"name":"Vascular Program, Institute for Cell Engineering, Departments of Pediatrics, Medicine, Oncology, Radiation Oncology, and Biological Chemistry, and McKusick\u2013Nathans 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 Integrated Physiology and Center for Systems Biology of O2 Sensing, University of Chicago, Chicago, IL 60637;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2011,1,31]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/wsbm.69"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.12.5510"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.2.149"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.114033"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.022634199"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2000.88.6.2287"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1042\/bse0430043"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI5912"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.11.1.72"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.9.4273"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2006.08.026"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1266"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI15496"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.07-1469"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-05-1695"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.21.3320"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1109\/10.959330"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(02)49317-2"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi049803f"},{"key":"e_1_3_3_20_2","first-page":"2607","article-title":"NADPH Oxidase 2 mediates intermittent hypoxia-induced mitochondrial complex I inhibition: Relevance to blood pressure changes in rats","volume":"11","author":"Khan SA","year":"2011","unstructured":"SA Khan, et al., NADPH Oxidase 2 mediates intermittent hypoxia-induced mitochondrial complex I inhibition: Relevance to blood pressure changes in rats. 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