RGD Reference Report - Inhibition of microRNA-1 attenuates hypoxia/re-oxygenation-induced apoptosis of cardiomyocytes by directly targeting Bcl-2 but not GADD45Beta. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Inhibition of microRNA-1 attenuates hypoxia/re-oxygenation-induced apoptosis of cardiomyocytes by directly targeting Bcl-2 but not GADD45Beta.

Authors: Zhai, Changlin  Tang, Guanmin  Peng, Lei  Hu, Huilin  Qian, Gang  Wang, Shijun  Yao, Jiankang  Zhang, Xiaoping  Fang, Ying  Yang, Shuang  Zhang, Xiumei 
Citation: Zhai C, etal., Am J Transl Res. 2015 Oct 15;7(10):1952-62. eCollection 2015.
RGD ID: 12911011
Pubmed: PMID:26692938   (View Abstract at PubMed)
PMCID: PMC4656771   (View Article at PubMed Central)

MicroRNAs are small non-coding RNAs that are able to regulate gene expression and play important roles in some biological and pathological processes, including the myocardial ischemia/reperfusion (I/R) injury. Recent findings demonstrated that miR-1 exacerbated I/R-induced injury. This study was to investigate theanti-apoptotic property of miR-1 inhibition and the potential regulatory mechanism. Results showed miR-1 expression reduced in the heart of rats undergoing myocardial I/R and the cardiomyocytes receiving hypoxia/reoxygenation (H/R) injury, but the serum miR-1 expression increased. The targets of miR-1 were predicted by cDNA microarray, and Bcl-2 and GADD45ß were selected as candidate targets. Western blot assay and qPCR showed Bcl-2 and GADD45ß protein and mRNA expressions increased after I/R injury and H/R injury. Bcl-2 was a direct target of miR-1 as shown in previous studies. Luciferase assay and Western blot assay revealed GADD45ß was a direct target of miR-1, and miR-1 suppressed GADD45ß expression via binding to its 3'UTR. Furthermore, miR-1 inhibition increased Bcl-2 expression and reduced IA/AAR (infarct area/area at risk) ratio and cell apoptosis in rats undergoing myocardial I/R as well as in cardiomyocytes receiving H/R injury. Importantly, Bcl-2 knockdown restored these consequences following miR-1 inhibition. However, GADD45ß knockdown reduced IA/AAR ratio and cell apoptosis in vivo and in vitro, but failed torestore above consequences after miR-1 inhibition. In conclusion miR-1 inhibition protects against H/R-induced apoptosis of myocytes by directly targeting Bcl-2 but not GADD45ß.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Bcl2Ratnegative regulation of cardiac muscle cell apoptotic process involved_inIMP PMID:26692938BHF-UCL 

Objects Annotated

Genes (Rattus norvegicus)
Bcl2  (BCL2, apoptosis regulator)


Additional Information