{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:43:02Z","timestamp":1791272582327,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2011,8,24]],"date-time":"2011-08-24T00:00:00Z","timestamp":1314144000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2011,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Sleep\u2010disordered breathing with recurrent apnea is associated with intermittent hypoxia (IH). Cardiovascular morbidities caused by IH are triggered by increased generation of reactive oxygen species (ROS) by pro\u2010oxidant enzymes, especially NADPH oxidase\u20102 (Nox2). Previous studies showed that (i) IH activates hypoxia\u2010inducible factor 1 (HIF\u20101) in a ROS\u2010dependent manner and (ii) HIF\u20101 is required for IH\u2010induced ROS generation, indicating the existence of a feed\u2010forward mechanism. In the present study, using multiple pharmacological and genetic approaches, we investigated whether IH\u2010induced expression of Nox2 is mediated by HIF\u20101 in the central and peripheral nervous system of mice as well as in cultured cells. IH increased Nox2 mRNA, protein, and enzyme activity in PC12 pheochromocytoma cells as well as in wild\u2010type mouse embryonic fibroblasts (MEFs). This effect was abolished or attenuated by blocking HIF\u20101 activity through RNA interference or pharmacologic inhibition (digoxin or YC\u20101) or by genetic knockout of HIF\u20101\u03b1 in MEFs. Increasing HIF\u20101\u03b1 expression by treating PC 12 cells with the iron chelator deferoxamine for 20\u2009h or by transfecting them with HIF\u20101alpha expression vector increased Nox2 expression and enzyme activity. Exposure of wild\u2010type mice to IH (8\u2009h\/day for 10 days) up\u2010regulated Nox2 mRNA expression in brain cortex, brain stem, and carotid body but not in cerebellum. IH did not induce Nox2 expression in cortex, brainstem, carotid body, or cerebellum of <jats:italic>Hif1a<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mice, which do not manifest increased ROS or cardiovascular morbidities in response to IH. These results establish a pathogenic mechanism linking HIF\u20101, ROS generation, and cardiovascular pathology in response to IH. J. Cell. Physiol. 226: 2925\u20132933, 2011. \u00a9 2011 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.22640","type":"journal-article","created":{"date-parts":[[2011,2,1]],"date-time":"2011-02-01T14:30:58Z","timestamp":1296570658000},"page":"2925-2933","source":"Crossref","is-referenced-by-count":185,"title":["Hypoxia\u2010inducible factor 1 mediates increased expression of NADPH oxidase\u20102 in response to intermittent hypoxia"],"prefix":"10.1002","volume":"226","author":[{"given":"Guoxiang","family":"Yuan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shakil 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