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.Základní údaje
Originální název
Hypoxia favors myosin heavy chain beta gene expression in an Hif-1alpha-dependent manner
Autoři
BINÓ, Lucia (703 Slovensko, domácí), Jiřina PROCHÁZKOVÁ (203 Česká republika, domácí), Katarzyna Anna RADASZKIEWICZ (616 Polsko, domácí), Jan KUČERA (203 Česká republika, domácí), Jana KUDOVÁ (203 Česká republika, domácí), Jiří PACHERNÍK (203 Česká republika, domácí) a Lukáš KUBALA (203 Česká republika, garant, domácí)
Vydání
Oncotarget, New York, Impact Journals, 2017, 1949-2553
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Obor
10601 Cell biology
Stát vydavatele
Spojené státy
Utajení
není předmětem státního či obchodního tajemství
Impakt faktor
Impact factor: 5.168 v roce 2016
Kód RIV
RIV/00216224:14310/17:00098086
Organizační jednotka
Přírodovědecká fakulta
UT WoS
000413030900026
Klíčová slova anglicky
mouse; heart; myosin heavy chain; fetal gene program; hypoxia
Příznaky
Mezinárodní význam, Recenzováno
Změněno: 5. 4. 2018 09:53, Ing. Nicole Zrilić
Anotace
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.