BINÓ, Lucia, Jiřina PROCHÁZKOVÁ, Katarzyna Anna RADASZKIEWICZ, Jan KUČERA, Jana KUDOVÁ, Jiří PACHERNÍK and Lukáš KUBALA. Hypoxia favors myosin heavy chain beta gene expression in an Hif-1alpha-dependent manner. Oncotarget. New York: Impact Journals, 2017, vol. 8, No 48, p. 83684-83697. ISSN 1949-2553. Available from: https://dx.doi.org/10.18632/oncotarget.19016.
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Basic information
Original name Hypoxia favors myosin heavy chain beta gene expression in an Hif-1alpha-dependent manner
Authors BINÓ, Lucia (703 Slovakia, belonging to the institution), Jiřina PROCHÁZKOVÁ (203 Czech Republic, belonging to the institution), Katarzyna Anna RADASZKIEWICZ (616 Poland, belonging to the institution), Jan KUČERA (203 Czech Republic, belonging to the institution), Jana KUDOVÁ (203 Czech Republic, belonging to the institution), Jiří PACHERNÍK (203 Czech Republic, belonging to the institution) and Lukáš KUBALA (203 Czech Republic, guarantor, belonging to the institution).
Edition Oncotarget, New York, Impact Journals, 2017, 1949-2553.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 10601 Cell biology
Country of publisher United States of America
Confidentiality degree is not subject to a state or trade secret
WWW URL URL
Impact factor Impact factor: 5.168 in 2016
RIV identification code RIV/00216224:14310/17:00098086
Organization unit Faculty of Science
Doi http://dx.doi.org/10.18632/oncotarget.19016
UT WoS 000413030900026
Keywords in English mouse; heart; myosin heavy chain; fetal gene program; hypoxia
Tags NZ, rivok
Tags International impact, Reviewed
Changed by Changed by: Ing. Nicole Zrilić, učo 240776. Changed: 5/4/2018 09:53.
Abstract
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.
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