pubmed-article:15569687 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:15569687 | lifeskim:mentions | umls-concept:C0007634 | lld:lifeskim |
pubmed-article:15569687 | lifeskim:mentions | umls-concept:C2349001 | lld:lifeskim |
pubmed-article:15569687 | lifeskim:mentions | umls-concept:C0681850 | lld:lifeskim |
pubmed-article:15569687 | lifeskim:mentions | umls-concept:C1706203 | lld:lifeskim |
pubmed-article:15569687 | lifeskim:mentions | umls-concept:C2697811 | lld:lifeskim |
pubmed-article:15569687 | lifeskim:mentions | umls-concept:C0006772 | lld:lifeskim |
pubmed-article:15569687 | lifeskim:mentions | umls-concept:C0215848 | lld:lifeskim |
pubmed-article:15569687 | lifeskim:mentions | umls-concept:C0242184 | lld:lifeskim |
pubmed-article:15569687 | lifeskim:mentions | umls-concept:C0441655 | lld:lifeskim |
pubmed-article:15569687 | lifeskim:mentions | umls-concept:C0040649 | lld:lifeskim |
pubmed-article:15569687 | lifeskim:mentions | umls-concept:C1550501 | lld:lifeskim |
pubmed-article:15569687 | lifeskim:mentions | umls-concept:C0596235 | lld:lifeskim |
pubmed-article:15569687 | lifeskim:mentions | umls-concept:C0205267 | lld:lifeskim |
pubmed-article:15569687 | lifeskim:mentions | umls-concept:C1879547 | lld:lifeskim |
pubmed-article:15569687 | pubmed:issue | 6 | lld:pubmed |
pubmed-article:15569687 | pubmed:dateCreated | 2005-2-7 | lld:pubmed |
pubmed-article:15569687 | pubmed:abstractText | Intermittent hypoxia (IH) occurs in many pathological conditions. However, very little is known about the molecular mechanisms associated with IH. Hypoxia-inducible factor 1 (HIF-1) mediates transcriptional responses to continuous hypoxia. In the present study, we investigated whether IH activates HIF-1 and, if so, which signaling pathways are involved. PC12 cells were exposed to either to 20% O2 (non-hypoxic control) or to 60 cycles consisting of 30 s at 1.5% O2, followed by 4 min at 20% O2 (IH). Western blot analysis revealed significant increases in HIF-1alpha protein in nuclear extracts of cells subjected to IH. Expression of a HIF-1-dependent reporter gene was increased 3-fold in cells subjected to IH. Although IH induced the activation of ERK1, ERK2, JNK, PKC-alpha, and PKC-gamma, inhibitors of these kinases and of phosphatidylinositol 3-kinase did not block HIF-1-mediated reporter gene expression induced by IH, indicating that signaling via these kinases was not required. In contrast, addition of the intracellular Ca2+ chelator BAPTA-AM or the Ca2+/calmodulin-dependent (CaM) kinase inhibitor KN93 blocked reporter gene activation in response to IH. CaM kinase activity was increased 5-fold in cells subjected to IH. KN 93 prevented IH-induced transactivation mediated by HIF-1alpha, and its coactivator p300, which was phosphorylated by CaM kinase II in vitro. Expression of the HIF-1-regulated gene encoding tyrosine hydroxylase was induced by IH and this effect was blocked by KN93. These observations suggest that IH induces HIF-1 transcriptional activity via a novel signaling pathway involving CaM kinase. | lld:pubmed |
pubmed-article:15569687 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:15569687 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:15569687 | pubmed:language | eng | lld:pubmed |
pubmed-article:15569687 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:15569687 | pubmed:citationSubset | IM | lld:pubmed |
pubmed-article:15569687 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:15569687 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:15569687 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:15569687 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:15569687 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:15569687 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:15569687 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:15569687 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:15569687 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:15569687 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:15569687 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:15569687 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:15569687 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:15569687 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:15569687 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:15569687 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:15569687 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:15569687 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:15569687 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:15569687 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:15569687 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:15569687 | pubmed:month | Feb | lld:pubmed |
pubmed-article:15569687 | pubmed:issn | 0021-9258 | lld:pubmed |
pubmed-article:15569687 | pubmed:author | pubmed-author:SemenzaGregg... | lld:pubmed |
pubmed-article:15569687 | pubmed:author | pubmed-author:PrabhakarNand... | lld:pubmed |
pubmed-article:15569687 | pubmed:author | pubmed-author:YuanGuoxiangG | lld:pubmed |
pubmed-article:15569687 | pubmed:author | pubmed-author:NanduriJayasr... | lld:pubmed |
pubmed-article:15569687 | pubmed:author | pubmed-author:BhaskerC... | lld:pubmed |
pubmed-article:15569687 | pubmed:issnType | Print | lld:pubmed |
pubmed-article:15569687 | pubmed:day | 11 | lld:pubmed |
pubmed-article:15569687 | pubmed:volume | 280 | lld:pubmed |
pubmed-article:15569687 | pubmed:owner | NLM | lld:pubmed |
pubmed-article:15569687 | pubmed:authorsComplete | Y | lld:pubmed |
pubmed-article:15569687 | pubmed:pagination | 4321-8 | lld:pubmed |
pubmed-article:15569687 | pubmed:dateRevised | 2010-11-18 | lld:pubmed |
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pubmed-article:15569687 | pubmed:year | 2005 | lld:pubmed |
pubmed-article:15569687 | pubmed:articleTitle | Ca2+/calmodulin kinase-dependent activation of hypoxia inducible factor 1 transcriptional activity in cells subjected to intermittent hypoxia. | lld:pubmed |
pubmed-article:15569687 | pubmed:affiliation | Department of Physiology & Biophysics, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA. | lld:pubmed |