RGD Reference Report - MicroRNA-17-mediated down-regulation of apoptotic protease activating factor 1 attenuates apoptosome formation and subsequent apoptosis of cardiomyocytes. - Rat Genome Database

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MicroRNA-17-mediated down-regulation of apoptotic protease activating factor 1 attenuates apoptosome formation and subsequent apoptosis of cardiomyocytes.

Authors: Song, S  Seo, HH  Lee, SY  Lee, CY  Lee, J  Yoo, KJ  Yoon, C  Choi, E  Hwang, KC  Lee, S 
Citation: Song S, etal., Biochem Biophys Res Commun. 2015 Sep 18;465(2):299-304. doi: 10.1016/j.bbrc.2015.08.028. Epub 2015 Aug 8.
RGD ID: 11079191
Pubmed: PMID:26265044   (View Abstract at PubMed)
DOI: DOI:10.1016/j.bbrc.2015.08.028   (Journal Full-text)

Heart diseases such as myocardial infarction (MI) can damage individual cardiomyocytes, leading to the activation of cell death programs. The most scrutinized type of cell death in the heart is apoptosis, and one of the key events during the propagation of apoptotic signaling is the formation of apoptosomes, which relay apoptotic signals by activating caspase-9. As one of the major components of apoptosomes, apoptotic protease activating factor 1 (Apaf-1) facilitates the formation of apoptosomes containing cytochrome c (Cyto-c) and deoxyadenosine triphosphate (dATP). Thus, it may be possible to suppress the activation of the apoptotic program by down-regulating the expression of Apaf-1 using miRNAs. To validate this hypothesis, we selected a number of candidate miRNAs that were expected to target Apaf-1 based on miRNA target prediction databases. Among these candidate miRNAs, we empirically identified miR-17 as a novel Apaf-1-targeting miRNA. The delivery of exogenous miR-17 suppressed Apaf-1 expression and consequently attenuated formation of the apoptosome complex containing caspase-9, as demonstrated by co-immunoprecipitation and immunocytochemistry. Furthermore, miR-17 suppressed the cleavage of procaspase-9 and the subsequent activation of caspase-3, which is downstream of activated caspase-9. Cell viability tests also indicated that miR-17 pretreatment significantly prevented the norepinephrine-induced apoptosis of cardiomyocytes, suggesting that down-regulation of apoptosome formation may be an effective strategy to prevent cellular apoptosis. These results demonstrate the potential of miR-17 as an effective anti-apoptotic agent.



Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Apaf1Ratapoptosome part_ofIDA PMID:26265044BHF-UCL 

Objects Annotated

Genes (Rattus norvegicus)
Apaf1  (apoptotic peptidase activating factor 1)


Additional Information