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transcription factor, induced by hypoxia, that is composed of HIF-1a and HIF-1b protein subunits. It binds to promoter/enhancer elements and stimulates the transcription of hypoxia-inducible target genes, including glucose transporter-1 and the glycolytic enzymes. Because HIF-1 activation might promote cell survival in hypoxic tissues, we studied the effect of permanent middle cerebral artery occlusion on the expression of HIF-1a, HIF-1b and several HIF-1 target genes in adult rat brain. After focal ischaemia, mRNAs encoding HIF-1a, glucose transporter-1 and several glycolytic enzymes were up-regulated in the peri-infarct penumbra. This was observed by 7.5 h after the onset of ischaemia and increased further at 19 and 24 h. Regional cerebral blood¯ow was moderately decreased at 1 and 24 h after the ischaemia in areas of HIF-1 and HIF-1 target gene induction. Because hypoxia induces HIF-1 in other tissues, systemic hypoxia (6% O 2 for 4.5 h) was also shown to increase HIF-1a protein expression in the adult rat brain. It is proposed that decreased blood¯ow to the penumbra decreases the supply of oxygen and that this induces HIF-1 and its target genes. This is the ®rst study to show induction of HIF-1 after focal ischaemia in brain. Increased expression of HIF-1 target genes as a result of HIF-1 activation by hypoxia may contribute to tissue viability in the hypoxic/ischaemic penumbra by increasing glucose transport and glycolysis.","publication_date":"1999,,","publication_name":"European Journal of Neuroscience","grobid_abstract_attachment_id":"45333733"},"document_type":"paper","pre_hit_view_count_baseline":null,"quality":"high","language":"en","title":"Induction of hypoxia-inducible factor-1 (HIF-1) and its target genes following focal ischaemia in rat brain","broadcastable":false,"draft":null,"has_indexable_attachment":true,"indexable":true}}["work"]; window.loswp.workCoauthors = [32675304]; window.loswp.locale = "en"; window.loswp.countryCode = "SG"; window.loswp.cwvAbTestBucket = ""; window.loswp.designVariant = "ds_vanilla"; window.loswp.fullPageMobileSutdModalVariant = "control"; window.loswp.useOptimizedScribd4genScript = false; window.loswp.appleClientId = 'edu.academia.applesignon';</script><script 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class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="63134697" href="https://independent.academia.edu/HermannEinsele">Hermann Einsele</a><span>, </span><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="32699700" href="https://deu.academia.edu/HarunSaid">Harun M ( U A Y A D ) Said</a><span>, </span><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="39211172" href="https://uni-wue.academia.edu/AstridKatzer">Astrid Katzer</a></div><p class="ds-related-work--metadata ds2-5-body-xs">2007</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Modulation of Glucose Metabolism Inhibits Hypoxic Accumulation of Hypoxia-Inducible Factor-1α (HIF-1α)","attachmentId":45273170,"attachmentType":"pdf","work_url":"https://www.academia.edu/13493056/Modulation_of_Glucose_Metabolism_Inhibits_Hypoxic_Accumulation_of_Hypoxia_Inducible_Factor_1%CE%B1_HIF_1%CE%B1_","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/13493056/Modulation_of_Glucose_Metabolism_Inhibits_Hypoxic_Accumulation_of_Hypoxia_Inducible_Factor_1%CE%B1_HIF_1%CE%B1_"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="1" data-entity-id="31547300" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/31547300/HIF_1_is_expressed_in_normoxic_tissue_and_displays_an_organ_specific_regulation_under_systemic_hypoxia">HIF-1 is expressed in normoxic tissue and displays an organ-specific regulation under systemic hypoxia</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="60441002" href="https://independent.academia.edu/DesleyNeil">Desley Neil</a></div><p class="ds-related-work--metadata ds2-5-body-xs">FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2001</p><p class="ds-related-work--abstract ds2-5-body-sm">Adaptation to hypoxia is regulated by hypoxia-inducible factor 1 (HIF-1), a heterodimeric transcription factor consisting of an oxygen-regulated alpha subunit and a constitutively expressed beta subunit. Although HIF-1 is regulated mainly by oxygen tension through the oxygen-dependent degradation of its alpha subunit, in vitro it can also be modulated by cytokines, hormones and genetic alterations. To investigate HIF-1 activation in vivo, we determined the spatial and temporal distribution of HIF-1 in healthy mice subjected to varying fractions of inspiratory oxygen. Immunohistochemical examination of brain, kidney, liver, heart, and skeletal muscle revealed that HIF-1alpha is present in mice kept under normoxic conditions and is further increased in response to systemic hypoxia. Moreover, immunoblot analysis showed that the kinetics of HIF-1alpha expression varies among different organs. In liver and kidney, HIF-1alpha reaches maximal levels after 1 h and gradually decreases to bas...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"HIF-1 is expressed in normoxic tissue and displays an organ-specific regulation under systemic hypoxia","attachmentId":51887828,"attachmentType":"pdf","work_url":"https://www.academia.edu/31547300/HIF_1_is_expressed_in_normoxic_tissue_and_displays_an_organ_specific_regulation_under_systemic_hypoxia","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/31547300/HIF_1_is_expressed_in_normoxic_tissue_and_displays_an_organ_specific_regulation_under_systemic_hypoxia"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="2" data-entity-id="19792179" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/19792179/Oxygen_treatment_following_experimental_hypoxia_ischemia_in_neonatal_rats_alters_the_expression_of_HIF_1_alpha_and_its_downstream_target_genes">Oxygen treatment following experimental hypoxia-ischemia in neonatal rats alters the expression of HIF-1 alpha and its downstream target genes</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="40523166" href="https://independent.academia.edu/JulianCahill">Julian Cahill</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Applied …, 2006</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Oxygen treatment following experimental hypoxia-ischemia in neonatal rats alters the expression of HIF-1 alpha and its downstream target genes","attachmentId":42016520,"attachmentType":"pdf","work_url":"https://www.academia.edu/19792179/Oxygen_treatment_following_experimental_hypoxia_ischemia_in_neonatal_rats_alters_the_expression_of_HIF_1_alpha_and_its_downstream_target_genes","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/19792179/Oxygen_treatment_following_experimental_hypoxia_ischemia_in_neonatal_rats_alters_the_expression_of_HIF_1_alpha_and_its_downstream_target_genes"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="3" data-entity-id="117106265" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/117106265/HIF_1%CE%B1_is_neuroprotective_during_the_early_phases_of_mild_hypoxia_in_rat_cortical_neurons">HIF-1α is neuroprotective during the early phases of mild hypoxia in rat cortical neurons</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="215594584" href="https://independent.academia.edu/BeatrizLopez267">Beatriz Lopez</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Experimental Neurology, 2012</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"HIF-1α is neuroprotective during the early phases of mild hypoxia in rat cortical neurons","attachmentId":113052745,"attachmentType":"pdf","work_url":"https://www.academia.edu/117106265/HIF_1%CE%B1_is_neuroprotective_during_the_early_phases_of_mild_hypoxia_in_rat_cortical_neurons","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/117106265/HIF_1%CE%B1_is_neuroprotective_during_the_early_phases_of_mild_hypoxia_in_rat_cortical_neurons"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="4" data-entity-id="19792182" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/19792182/Oxygen_treatment_after_experimental_hypoxia_ischemia_in_neonatal_rats_alters_the_expression_of_HIF_1_and_its_downstream_target_genes">Oxygen treatment after experimental hypoxia-ischemia in neonatal rats alters the expression of HIF-1 and its downstream target genes</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="40523166" href="https://independent.academia.edu/JulianCahill">Julian Cahill</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Applied Physiology, 2006</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Oxygen treatment after experimental hypoxia-ischemia in neonatal rats alters the expression of HIF-1 and its downstream target genes","attachmentId":42016494,"attachmentType":"pdf","work_url":"https://www.academia.edu/19792182/Oxygen_treatment_after_experimental_hypoxia_ischemia_in_neonatal_rats_alters_the_expression_of_HIF_1_and_its_downstream_target_genes","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/19792182/Oxygen_treatment_after_experimental_hypoxia_ischemia_in_neonatal_rats_alters_the_expression_of_HIF_1_and_its_downstream_target_genes"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="5" data-entity-id="24744858" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/24744858/REST_mediates_resolution_of_HIF_dependent_gene_expression_in_prolonged_hypoxia_OPEN">REST mediates resolution of HIF-dependent gene expression in prolonged hypoxia OPEN</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="47951587" href="https://independent.academia.edu/MManresa">M. Manresa</a><span>, </span><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="32999621" href="https://gulbenkian.academia.edu/MiguelCavadas">Miguel Cavadas</a><span>, </span><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="47811246" href="https://kernkracht.academia.edu/MarionMesnieres">Marion Mesnieres</a></div><p class="ds-related-work--abstract ds2-5-body-sm">The hypoxia-inducible factor (HIF) is a key regulator of the cellular response to hypoxia which promotes oxygen delivery and metabolic adaptation to oxygen deprivation. However, the degree and duration of HIF-1α expression in hypoxia must be carefully balanced within cells in order to avoid unwanted side effects associated with excessive activity. The expression of HIF-1α mRNA is suppressed in prolonged hypoxia, suggesting that the control of HIF1A gene transcription is tightly regulated by negative feedback mechanisms. Little is known about the resolution of the HIF-1α protein response and the suppression of HIF-1α mRNA in prolonged hypoxia. Here, we demonstrate that the Repressor Element 1-Silencing Transcription factor (REST) binds to the HIF-1α promoter in a hypoxia-dependent manner. Knockdown of REST using RNAi increases the expression of HIF-1α mRNA, protein and transcriptional activity. Furthermore REST knockdown increases glucose consumption and lactate production in a HIF-1α-(but not HIF-2α-) dependent manner. Finally, REST promotes the resolution of HIF-1α protein expression in prolonged hypoxia. In conclusion, we hypothesize that REST represses transcription of HIF-1α in prolonged hypoxia, thus contributing to the resolution of the HIF-1α response. Hypoxia is a key microenvironmental feature of a range of physiological and pathophysiological conditions including embryonic development, exercise, cancer, ischemia and inflammation 1. Adaptive transcriptional pathways have evolved to help an organism deal with the metabolic threat posed by hypoxia. The best-described transcrip-tional adaptive response in cells is mediated by the hypoxia inducible factor (HIF) signalling pathway, which up-regulates genes which restore oxygen and energy homeostasis 2–4. In normoxia, HIFα is hydroxylated by the prolyl-hydroxylase domain (PHD) family of dioxygenases targeting it for proteosomal degradation 5. This process is reversed in hypoxia and HIFα is stabilized, dimerizes with HIFβ and binds to hypoxia response elements (HRE) in the regulatory regions of target genes 6. HIF drives an adaptive response to hypoxia by promoting the expression of genes including those that regulate erythropoiesis, angiogenesis and glycolysis 6. However in cancer, HIF signalling can be maladaptive and contribute to tumour survival 1. Because of the potentially deleterious effects of over-activation of the HIF pathway, a resolution mechanism is required to resolve its activity in prolonged hypoxia. In the absence of such a resolving mechanism, deleterious consequences such as pathologic angiogenesis and excessive haematocrit due to chronic HIF stabilization may occur 7–9. While several regulators of HIF expression exist, only a few have been shown to be involved in the resolution of the HIF response to hypoxia. PHD2 and PHD3 are, for example, part of an auto-regulatory mechanism, whereby HIF-1α which is stabilized in hypoxia, transcriptionally induces the expression of EGLN1 and EGLN3 genes coding for PHD2 and PHD3 proteins respectively 10–12. The increased expression of the PHD enzymes in turn promotes HIFα hydroxylation, and reduction of its expression in prolonged hypoxia 10. Less is known about the control of HIF1A mRNA stability 11. Interestingly, while HIF-1α protein is transiently up-regulated in hypoxia, the mRNA is frequently found to be repressed 12–15. This transcript attenuation can be conveyed through mRNA destabilization by the protein tristetraprolin in endothelial cells 14 and by miR155 in intestinal epithelial cells 12 .</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"REST mediates resolution of HIF-dependent gene expression in prolonged hypoxia OPEN","attachmentId":45073645,"attachmentType":"pdf","work_url":"https://www.academia.edu/24744858/REST_mediates_resolution_of_HIF_dependent_gene_expression_in_prolonged_hypoxia_OPEN","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/24744858/REST_mediates_resolution_of_HIF_dependent_gene_expression_in_prolonged_hypoxia_OPEN"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="6" data-entity-id="18101247" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/18101247/Widespread_hypoxia_inducible_expression_of_HIF_2alpha_in_distinct_cell_populations_of_different_organs">Widespread, hypoxia-inducible expression of HIF-2alpha in distinct cell populations of different organs</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="38055361" href="https://independent.academia.edu/StefanoMandriota">Stefano Mandriota</a></div><p class="ds-related-work--metadata ds2-5-body-xs">The FASEB Journal, 2002</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Widespread, hypoxia-inducible expression of HIF-2alpha in distinct cell populations of different organs","attachmentId":42053732,"attachmentType":"pdf","work_url":"https://www.academia.edu/18101247/Widespread_hypoxia_inducible_expression_of_HIF_2alpha_in_distinct_cell_populations_of_different_organs","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/18101247/Widespread_hypoxia_inducible_expression_of_HIF_2alpha_in_distinct_cell_populations_of_different_organs"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="7" data-entity-id="29510709" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/29510709/Brain_Specific_Knock_Out_of_Hypoxia_Inducible_Factor_1_Reduces_Rather_Than_Increases_Hypoxic_Ischemic_Damage">Brain-Specific Knock-Out of Hypoxia-Inducible Factor-1 Reduces Rather Than Increases Hypoxic-Ischemic Damage</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="55775890" href="https://independent.academia.edu/CarroleeBarlow">Carrolee Barlow</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Neuroscience, 2005</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Brain-Specific Knock-Out of Hypoxia-Inducible Factor-1 Reduces Rather Than Increases Hypoxic-Ischemic Damage","attachmentId":49948246,"attachmentType":"pdf","work_url":"https://www.academia.edu/29510709/Brain_Specific_Knock_Out_of_Hypoxia_Inducible_Factor_1_Reduces_Rather_Than_Increases_Hypoxic_Ischemic_Damage","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/29510709/Brain_Specific_Knock_Out_of_Hypoxia_Inducible_Factor_1_Reduces_Rather_Than_Increases_Hypoxic_Ischemic_Damage"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="8" data-entity-id="56453480" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/56453480/Hypoxia_and_HIF_Signaling_One_Axis_with_Divergent_Effects">Hypoxia and HIF Signaling: One Axis with Divergent Effects</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="47395847" href="https://independent.academia.edu/SimonaFontana4">Simona Fontana</a></div><p class="ds-related-work--metadata ds2-5-body-xs">International Journal of Molecular Sciences</p><p class="ds-related-work--abstract ds2-5-body-sm">The correct concentration of oxygen in all tissues is a hallmark of cellular wellness, and the negative regulation of oxygen homeostasis is able to affect the cells and tissues of the whole organism. The cellular response to hypoxia is characterized by the activation of multiple genes involved in many biological processes. Among them, hypoxia-inducible factor (HIF) represents the master regulator of the hypoxia response. The active heterodimeric complex HIF α/β, binding to hypoxia-responsive elements (HREs), determines the induction of at least 100 target genes to restore tissue homeostasis. A growing body of evidence demonstrates that hypoxia signaling can act by generating contrasting responses in cells and tissues. Here, this dual and controversial role of hypoxia and the HIF signaling pathway is discussed, with particular reference to the effects induced on the complex activities of the immune system and on mechanisms determining cell and tissue responses after an injury in both...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Hypoxia and HIF Signaling: One Axis with Divergent Effects","attachmentId":71833017,"attachmentType":"pdf","work_url":"https://www.academia.edu/56453480/Hypoxia_and_HIF_Signaling_One_Axis_with_Divergent_Effects","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/56453480/Hypoxia_and_HIF_Signaling_One_Axis_with_Divergent_Effects"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="9" data-entity-id="64869293" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/64869293/Overexpression_of_bHLH_domain_of_HIF_1_failed_to_inhibit_the_HIF_1_transcriptional_activity_in_hypoxia">Overexpression of bHLH domain of HIF-1 failed to inhibit the HIF-1 transcriptional activity in hypoxia</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="5475052" href="https://independent.academia.edu/RezaFalak">Reza Falak</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Biological Research, 2020</p><p class="ds-related-work--abstract ds2-5-body-sm">Background Hypoxia inducible factor-1 (HIF-1) is considered as the most activated transcriptional factor in response to low oxygen level or hypoxia. HIF-1 binds the hypoxia response element (HRE) sequence in the promoter of different genes, mainly through the bHLH domain and activates the transcription of genes, especially those involved in angiogenesis and EMT. Considering the critical role of bHLH in binding HIF-1 to the HRE sequence, we hypothesized that bHLH could be a promising candidate to be targeted in hypoxia condition. Methods We inserted an inhibitory bHLH (ibHLH) domain in a pIRES2-EGFP vector and transfected HEK293T cells with either the control vector or the designed construct. The ibHLH domain consisted of bHLH domains of both HIF-1a and Arnt, capable of competing with HIF-1 in binding to HRE sequences. The transfected cells were then treated with 200 µM of cobalt chloride (CoCl 2 ) for 48 h to induce hypoxia. Real-time PCR and western blot were performed to evaluate ...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Overexpression of bHLH domain of HIF-1 failed to inhibit the HIF-1 transcriptional activity in hypoxia","attachmentId":76702852,"attachmentType":"pdf","work_url":"https://www.academia.edu/64869293/Overexpression_of_bHLH_domain_of_HIF_1_failed_to_inhibit_the_HIF_1_transcriptional_activity_in_hypoxia","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/64869293/Overexpression_of_bHLH_domain_of_HIF_1_failed_to_inhibit_the_HIF_1_transcriptional_activity_in_hypoxia"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div></div></div><div class="ds-sticky-ctas--wrapper js-loswp-sticky-ctas hidden"><div class="ds-sticky-ctas--grid-container"><div class="ds-sticky-ctas--container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--sticky-ctas","attachmentId":45333733,"attachmentType":"pdf","workUrl":null}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--sticky-ctas","attachmentId":45333733,"attachmentType":"pdf","workUrl":null}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div></div></div><div class="ds-below-fold--grid-container"><div class="ds-work--container js-loswp-embedded-document"><div class="attachment_preview" data-attachment="Attachment_45333733" style="display: none"><div class="js-scribd-document-container"><div class="scribd--document-loading js-scribd-document-loader" style="display: block;"><img alt="Loading..." src="//a.academia-assets.com/images/loaders/paper-load.gif" /><p>Loading Preview</p></div></div><div style="text-align: center;"><div class="scribd--no-preview-alert js-preview-unavailable"><p>Sorry, preview is currently unavailable. 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class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/14730756/HIF_1_and_AP_1_Cooperate_to_Increase_Gene_Expression_in_Hypoxia_Role_of_MAP_Kinases">HIF-1 and AP-1 Cooperate to Increase Gene Expression in Hypoxia: Role of MAP Kinases</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="33692092" href="https://lambiotte.academia.edu/CarineMichiels">Carine Michiels</a></div><p class="ds-related-work--metadata ds2-5-body-xs">IUBMB Life (International Union of Biochemistry and Molecular Biology: Life), 2001</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"HIF-1 and AP-1 Cooperate to Increase Gene Expression in Hypoxia: Role of MAP 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Dadak</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Molecular and Cellular Biology, 2003</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Hypoxia-Induced Gene Expression Occurs Solely through the Action of Hypoxia-Inducible Factor 1 (HIF-1 ): Role of Cytoplasmic Trapping of HIF-2 ","attachmentId":52286028,"attachmentType":"pdf","work_url":"https://www.academia.edu/32020650/Hypoxia_Induced_Gene_Expression_Occurs_Solely_through_the_Action_of_Hypoxia_Inducible_Factor_1_HIF_1_Role_of_Cytoplasmic_Trapping_of_HIF_2_","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" 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ds2-5-body-sm ds2-5-body-link" data-author-id="40523166" href="https://independent.academia.edu/JulianCahill">Julian Cahill</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Applied Physiology, 2006</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Oxygen treatment after experimental hypoxia-ischemia in neonatal rats alters the expression of HIF-1α and its downstream target genes","attachmentId":109131491,"attachmentType":"pdf","work_url":"https://www.academia.edu/111658974/Oxygen_treatment_after_experimental_hypoxia_ischemia_in_neonatal_rats_alters_the_expression_of_HIF_1%CE%B1_and_its_downstream_target_genes","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a 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class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="238238475" href="https://independent.academia.edu/JorgeSoliz15">Jorge Soliz</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Experimental Biology, 2016</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"HIF1α and physiological responses to hypoxia are correlated in mice but not in rats","attachmentId":101049399,"attachmentType":"pdf","work_url":"https://www.academia.edu/100145840/HIF1%CE%B1_and_physiological_responses_to_hypoxia_are_correlated_in_mice_but_not_in_rats","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline 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href="https://independent.academia.edu/SheldonAnn">Ann Sheldon</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Pediatric Research, 2014</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Hypoxic preconditioning protection is eliminated in HIF-1α knockout mice subjected to neonatal hypoxia–ischemia","attachmentId":42073291,"attachmentType":"pdf","work_url":"https://www.academia.edu/21561811/Hypoxic_preconditioning_protection_is_eliminated_in_HIF_1%CE%B1_knockout_mice_subjected_to_neonatal_hypoxia_ischemia","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" 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href="https://ub.academia.edu/TomasSantalucia">Tomas Santalucia</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Biological Chemistry, 2010</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Extended Ischemia Prevents HIF1α Degradation at Reoxygenation by Impairing Prolyl-hydroxylation","attachmentId":67257806,"attachmentType":"pdf","work_url":"https://www.academia.edu/48840082/Extended_Ischemia_Prevents_HIF1%CE%B1_Degradation_at_Reoxygenation_by_Impairing_Prolyl_hydroxylation","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" 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class="ds-related-work--metadata ds2-5-body-xs">Cells</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Transcriptional Response to Hypoxia: The Role of HIF-1-Associated Co-Regulators","attachmentId":101587322,"attachmentType":"pdf","work_url":"https://www.academia.edu/100896151/Transcriptional_Response_to_Hypoxia_The_Role_of_HIF_1_Associated_Co_Regulators","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/100896151/Transcriptional_Response_to_Hypoxia_The_Role_of_HIF_1_Associated_Co_Regulators"><span class="ds2-5-text-link__content">View PDF</span><span 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