Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0151744 (
myocardial ischemia
)
31,282
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
MiRNAs are a class of endogenous, short, single-stranded, non-coding RNAs, which are tightly linked to cardiac disorders such as
myocardial ischemia
/reperfusion (I/R) injury.
MiR-34a
is known to be involved in the hypoxia-induced cardiomyocytes apoptosis. However, the molecular mechanisms are unclear. In the present study, we demonstrate that under low glucose supply, rat cardiomyocytes are susceptible to hypoxia. Under short-time hypoxia, cellular glucose uptake and lactate product are induced but under long-time hypoxia, the cellular glucose metabolism is suppressed. Interestingly, an adaptive up-regulation of
miR-34a
by long-time hypoxia was observed both
in vitro
and
in vivo
, leading to suppression of glycolysis in cardiomyocytes. We identified
lactate dehydrogenase-A
(
LDHA
) as a direct target of
miR-34a
, which binds to the 3'-UTR region of
LDHA
mRNA in cardiomyocytes. Moreover, inhibition of
miR-34a
attenuated hypoxia-induced cardiomyocytes dysfunction through restoration of glycolysis. The present study illustrates roles of
miR-34a
in the hypoxia-induced cardiomyocytes dysfunction and proposes restoration of glycolysis of dysfunctional cardiomyocytes by inhibiting
miR-34a
during I/R might be an effectively therapeutic approach against I/R injury.
...
PMID:Attenuation of
miR-34a
protects cardiomyocytes against hypoxic stress through maintenance of glycolysis. 2889 25