Hypoxia favors myosin heavy chain beta gene expression in an
Hif-1alpha-dependent manner

J 2017

Hypoxia favors myosin heavy chain beta gene expression in an Hif-1alpha-dependent manner

BINÓ, Lucia, Jiřina PROCHÁZKOVÁ, Katarzyna Anna RADASZKIEWICZ, Jan KUČERA, Jana KUDOVÁ et. al.

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

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10601 Cell biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

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

Abstract

V originále

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.

Citovat

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.

@article{1394033,
   author = {Binó, Lucia and Procházková, Jiřina and Radaszkiewicz, Katarzyna Anna and Kučera, Jan and Kudová, Jana and Pacherník, Jiří and Kubala, Lukáš},
   article_location = {New York},
   article_number = {48},
   doi = {http://dx.doi.org/10.18632/oncotarget.19016},
   keywords = {mouse; heart; myosin heavy chain; fetal gene program; hypoxia},
   language = {eng},
   issn = {1949-2553},
   journal = {Oncotarget},
   title = {Hypoxia favors myosin heavy chain beta gene expression in an Hif-1alpha-dependent manner},
   url = {https://www.researchgate.net/profile/Lucia_Bino/publications},
   volume = {8},
   year = {2017}
}

TY  - JOUR
ID  - 1394033
AU  - Binó, Lucia - Procházková, Jiřina - Radaszkiewicz, Katarzyna Anna - Kučera, Jan - Kudová, Jana - Pacherník, Jiří - Kubala, Lukáš
PY  - 2017
TI  - Hypoxia favors myosin heavy chain beta gene expression in an Hif-1alpha-dependent manner
JF  - Oncotarget
VL  - 8
IS  - 48
SP  - 83684-83697
EP  - 83684-83697
PB  - Impact Journals
SN  - 19492553
KW  - mouse
KW  - heart
KW  - myosin heavy chain
KW  - fetal gene program
KW  - hypoxia
UR  - https://www.researchgate.net/profile/Lucia_Bino/publications
N2  - 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.
ER  -

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. \textit{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.

Detailed Information on Publication Record