{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:24:25Z","timestamp":1791329065221,"version":"4.3.1"},"reference-count":34,"publisher":"American Society of Hematology","issue":"4","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The key player for adaptation to reduced oxygen availability is the transcription factor hypoxia-inducible factor 1 (HIF-1), composed of the redox-sensitive HIF-1\u03b1 and the constitutively expressed HIF-1\u03b2 subunits. Under normoxic conditions, HIF-1\u03b1 is rapidly degraded, whereas hypoxia, CoCl2, or desferroxamine promote protein stabilization, thus evoking its transcriptional activity. Because HIF-1 is regulated by reactive oxygen species, investigation of the impact of reactive nitrogen species was intended. By using different nitric oxide (NO) donors, dose- and time-dependent HIF-1\u03b1 accumulation in close correlation with the release of NO from chemically distinct NO donors was established. Intriguingly, small NO concentrations induced a faster but transient HIF-1\u03b1 accumulation than higher doses of the same NO donor. In contrast, NO attenuated up-regulation of HIF-1\u03b1 evoked by CoCl2 in a concentration- and time-dependent manner, whereas the desferroxamine-elicited HIF-1\u03b1 signal remained unaltered. To demonstrate an autocrine or paracrine signaling function of NO, we overexpressed the inducible NO synthase and used a coculture system of activated macrophages and tubular cells. Expression of the NO synthase induced HIF-1\u03b1 accumulation, which underscored the role of NO as an intracellular activator for HIF-1. In addition, macrophage-derived NO triggered HIF-1\u03b1 up-regulation in LLC-PK1 target cells, which points to intercellular signaling properties of NO in achieving HIF-1 accumulation. Our results show that NO does not only modulate the HIF-1 response under hypoxic conditions, but it also functions as a HIF-1 inducer. We conclude that accumulation of HIF-1 occurs during hypoxia but also under inflammatory conditions that are characterized by sustained NO formation.<\/jats:p>","DOI":"10.1182\/blood.v97.4.1009","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T08:47:58Z","timestamp":1027759678000},"page":"1009-1015","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":215,"title":["Accumulation of HIF-1\u03b1 under the influence of nitric oxide"],"prefix":"10.1182","volume":"97","author":[{"given":"Katrin Britta","family":"Sandau","sequence":"first","affiliation":[{"name":"From the University of Erlangen-Nu\u0308rnberg, Faculty of Medicine, Department of Medicine IV\u2014Experimental Division, and Nikolaus-Fiebiger Center, Clinical Project Group I, Erlangen, Germany; and the University of Essen, Institute of Physiology, Essen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Fandrey","sequence":"additional","affiliation":[{"name":"From the University of Erlangen-Nu\u0308rnberg, Faculty of Medicine, Department of Medicine IV\u2014Experimental Division, and Nikolaus-Fiebiger Center, Clinical Project Group I, Erlangen, Germany; and the University of Essen, Institute of Physiology, Essen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Bru\u0308ne","sequence":"additional","affiliation":[{"name":"From the University of Erlangen-Nu\u0308rnberg, Faculty of Medicine, Department of Medicine IV\u2014Experimental Division, and Nikolaus-Fiebiger Center, Clinical Project Group I, Erlangen, Germany; and the University of Essen, Institute of Physiology, Essen, 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