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Hypoxia favors myosin heavy chain beta gene expression in an Hif-1alpha-dependent manner
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SYSNO ASEP 0506842 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Hypoxia favors myosin heavy chain beta gene expression in an Hif-1alpha-dependent manner Author(s) Binó, Lucia (BFU-R) ORCID
Procházková, Jiřina (BFU-R) RID, ORCID
Radaszkiewicz, K. A. (CZ)
Kučera, J. (CZ)
Kudová, Jana (BFU-R) ORCID
Pachernik, J. (CZ)
Kubala, Lukáš (BFU-R) RID, ORCIDNumber of authors 7 Source Title OncoTarget. - : Impact Journals LLC - ISSN 1949-2553
Roč. 8, č. 48 (2017), s. 83684-83697Number of pages 14 s. Language eng - English Country US - United States Keywords inducible factor ; mammalian target ; human heart ; myocardial-ischemia Subject RIV FD - Oncology ; Hematology OECD category Oncology R&D Projects LD11015 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support BFU-R - RVO:68081707 UT WOS 000413030900026 DOI 10.18632/oncotarget.19016 Annotation The potentiation of the naturally limited regenerative capacity of the heart is dependent on an understanding of the mechanisms that are activated in response to pathological conditions such as hypoxia. Under these conditions, the expression of genes suggested to support cardiomyocyte survival and heart adaptation is triggered. Particularly important are changes in the expression of myosin heavy chain (MHC) isoforms. We propose here that alterations in the expression profiles of MHC genes are induced in response to hypoxia and are primarily mediated by hypoxia inducible factor (HIF). In in vitro models of mouse embryonic stem cell-derived cardiomyocytes, we showed that hypoxia (1% O-2) or the pharmacological stabilization of HIFs significantly increased MHCbeta (Myh7) gene expression. The key role of HIF-1alpha is supported by the absence of these effects in HIF-1alpha-deficient cells, even in the presence of HIF-2alpha. Interestingly, ChIP analysis did not confirm the direct interaction of HIF-1alpha with putative HIF response elements predicted in the MHCalpha and beta encoding DNA region. Further analyses showed the significant effect of the mTOR signaling inhibitor rapamycin in inducing Myh7 expression and a hypoxia-triggered reduction in the levels of antisense RNA transcripts associated with the Myh7 gene locus. Overall, the recognized and important role of HIF in the regulation of heart regenerative processes could be highly significant for the development of novel therapeutic interventions in heart failure. Workplace Institute of Biophysics Contact Jana Poláková, polakova@ibp.cz, Tel.: 541 517 244 Year of Publishing 2020 Electronic address http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=download&path%5B%5D=19016&path%5B%5D=60953
Number of the records: 1