{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:31:22Z","timestamp":1790832682481,"version":"4.1.0"},"reference-count":58,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Physiological Genomics"],"published-print":{"date-parts":[[2005,9,21]]},"abstract":"<jats:p>Hypoxia-inducible factor-1 (HIF-1) is a key regulator of the cellular hypoxic response. We previously showed that HIF-1 activation is essential for heat acclimation (AC) in Caenorhabditis elegans. Metabolic changes in AC rat hearts indicate HIF-1\u03b1 activation in mammals as well. Here we characterize the HIF-1\u03b1 profile and the transcriptional activation of its target genes following AC and following heat stress (HS) in hearts from nonacclimated (C; 24\u00b0C) and AC (34\u00b0C, 1 mo) rats. We used Western blot and immunohistochemistry to measure HIF-1\u03b1 levels and EMSA and RT-PCR\/quantitative RT-PCR to detect expression of the HIF-1\u03b1-targeted genes, including vascular endothelial growth factor ( Vegf), heme oxygenase-1 ( HO1), erythropoietin ( Epo), and Epo receptor ( EpoR). EpoR and Epo mRNA levels were measured to determine systemic effects in the kidneys and cross-tolerance effects in C and AC ischemic hearts (Langendorff, 75% ischemia, 40 min). The results demonstrated that 1) after AC, HIF-1\u03b1 protein levels were increased, 2) HS alone induced transient HIF-1\u03b1 upregulation, and 3) VEGF and HO1 mRNA levels increased after HS, with greater magnitude in the AC hearts. Epo mRNA in AC kidneys and EpoR mRNA in AC hearts were also elevated. In AC hearts, EpoR expression was markedly higher after HS or ischemia. Hearts from AC rats were dramatically protected against infarction after ischemia-perfusion. We conclude that HIF-1 contributes to the acclimation-ischemia cross-tolerance mechanism in the heart by induction of both chronic and inducible adaptive components.<\/jats:p>","DOI":"10.1152\/physiolgenomics.00279.2004","type":"journal-article","created":{"date-parts":[[2005,7,27]],"date-time":"2005-07-27T02:44:20Z","timestamp":1122432260000},"page":"79-88","source":"Crossref","is-referenced-by-count":127,"title":["HIF-1\u03b1-targeted pathways are activated by heat acclimation and contribute to acclimation-ischemic cross-tolerance in the heart"],"prefix":"10.1152","volume":"23","author":[{"given":"Alina","family":"Maloyan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luba","family":"Eli-Berchoer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregg L.","family":"Semenza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Gerstenblith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Stern","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Horowitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000012702.90501.8D"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000078635.89229.8A"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000127954.98131.23"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M001914200"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2002.17.5.581"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2828(01)90087-2"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(99)00077-5"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1999.276.2.R550"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00304.2002"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00577.2003"},{"key":"R11","unstructured":"Feldser D, Agani F, Iyer NV, Pak B, Ferreira G, and Semenza GL.Reciprocal positive regulation of hypoxia-inducible factor 1\u03b1 and insulin-like growth factor 2.Cancer Res59: 3915\u20133918, 1999."},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M203781200"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4565(99)00054-6"},{"key":"R14","unstructured":"Haddad JJ.Recombinant human interleukin (IL)-1\u03b2-mediated regulation of hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) stabilization, nuclear translocation and activation requires an antioxidant\/reactive oxygen species (ROS)-sensitive mechanism.Eur Cytokine Netw13: 250\u2013260, 2002."},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1007\/BF00585874"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1016\/S1095-6433(01)00500-1"},{"key":"R17","unstructured":"Horowitz M.Matching the heart to heat-induced circulatory load: heat-acclimatory responses.News Physiol Sci18: 215\u2013221, 2003."},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1007\/BF00374295"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1016\/0300-9629(83)90374-2"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00306.2004"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.2.149"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.30.17771"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M308197200"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110377200"},{"key":"R25","unstructured":"Kimura H, Weisz A, Kurashima Y, Hashimoto K, Ogura T, D'Acquisto F, Addeo R, Makuuchi M, Esumi H.Hypoxia response element of the human vascular endothelial growth factor gene mediates transcriptional regulation by nitric oxide: control of hypoxia-inducible factor-1 activity by nitric oxide.Blood95: 189\u2013197, 2000."},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000102937.50486.1B"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1038\/227680a0"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.12.3995-4004.2001"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1993.75.2.833"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1999.276.5.R1506"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2828(01)90285-8"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01122.2001"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E02-12-0791"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.27.1.4862"},{"key":"R35","unstructured":"Nagasawa J, Sato Y, Yamashita H, Ookawara T, Kizaki T, Habara Y, and Ohno H.Is heat acclimation able to increase whole-body sensitivity to insulin?Res Commun Chem Pathol Pharmacol84: 375\u2013378, 1994."},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209114200"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1124\/mol.58.6.1197"},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.23.14.4959-4971.2003"},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.01016"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.1016\/S1095-6433(02)00045-4"},{"key":"R41","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.17.11205"},{"key":"R42","doi-asserted-by":"crossref","unstructured":"Richard DE, Berra E, and Pouyssegur J.Nonhypoxic pathway mediates the induction of hypoxia-inducible factor 1\u03b1 in vascular smooth muscle cells.J Biol Chem275: 26765\u201326771, 2000.","DOI":"10.1016\/S0021-9258(19)61441-9"},{"key":"R43","unstructured":"Sawka MN, Wenger CB, and Pandolf KB.Thermoregulatory responses to acute exercise-heat stress and heat acclimation. In:Handbook of Physiology. Environmental Physiology.Bethesda, MD: Am Physiol Soc, 1996, sect. 4, vol. I, p. 157\u2013187."},{"key":"R44","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00001.2004"},{"key":"R45","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0403540101"},{"key":"R46","doi-asserted-by":"publisher","DOI":"10.1096\/fj.01-0125com"},{"key":"R47","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00058.2004"},{"key":"R48","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(03)01503-1"},{"key":"R49","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00179.2002"},{"key":"R50","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204152200"},{"key":"R51","unstructured":"Wenger RH.Cellular adaptation to hypoxia: O2-sensing protein hydroxylases, hypoxia-inducible transcription factors, and O2-regulated gene expression.FASEB J16: 1152\u20131162, 2002."},{"key":"R52","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03-1289fje"},{"key":"R53","doi-asserted-by":"crossref","unstructured":"Yu AY, Fri MG, Shimoda LA, Weiner CM, Stenmark K, and Semenza GL.Temporal, spatial, and oxygen-regulated expression of hypoxia-inducible factor-1 in the lung.Am J Physiol Lung Cell Mol Physiol275: L818\u2013L826, 1998.","DOI":"10.1152\/ajplung.1998.275.4.L818"},{"key":"R54","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.17.5085"},{"key":"R55","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2001.280.2.H909"},{"key":"R56","unstructured":"Zhong H, Chiles K, Feldser D, Laughner E, Hanrahan C, Georgescu MM, Simons JW, and Semenza GL.Modulation of hypoxia-inducible factor 1\u03b1 expression by the epidermal growth factor\/phosphatidylinositol 3-kinase\/PTEN\/AKT\/FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics.Cancer Res60: 1541\u20131545, 2000."},{"key":"R57","unstructured":"Zhong H, De Marzo AM, Laughner E, Lim M, Hilton DA, Zagzag D, Buechler P, Isaacs WB, Semenza GL, and Simons JW.Overexpression of hypoxia-inducible factor 1\u03b1 in common human cancers and their metastases.Cancer Res59: 5830\u20135835, 1999."},{"key":"R58","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M310164200"}],"container-title":["Physiological Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/physiolgenomics.00279.2004","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T02:25:39Z","timestamp":1626229539000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/physiolgenomics.00279.2004"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,9,21]]},"references-count":58,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2005,9,21]]}},"alternative-id":["10.1152\/physiolgenomics.00279.2004"],"URL":"https:\/\/doi.org\/10.1152\/physiolgenomics.00279.2004","relation":{},"ISSN":["1094-8341","1531-2267"],"issn-type":[{"value":"1094-8341","type":"print"},{"value":"1531-2267","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,9,21]]}}}