Increased miR1873p expression after cerebral ischemia/reperfusion induces apoptosis via initiation of endoplasmic reticulum stress.
Neurosci Lett
; 759: 135947, 2021 08 10.
Article
em En
| MEDLINE
| ID: mdl-34015413
ABSTRACT
Ischemia/reperfusion (I/R) injury induces activation of the endoplasmic reticulum stress (ERS) pathway, accompanied by an increase in apoptosis. Multiple microRNAs (miRNAs/miRs) are dysregulated during I/R and contribute to I/R-induced injury. miRNAs act as suppressors of gene expression and negatively regulate gene expression by targeting the protein-coding sequence (CDS) of specific target mRNAs. Seipin is an endoplasmic reticulum protein that has recently been associated with ERS. We previously reported that seipin is the target gene of miR1873p. Therefore, we explored the involvement of miR-187-3p in I/R-induced ERS via the regulation of seipin. A rat MCAO/R model was established by 1â¯h of occlusion and 24â¯h reperfusion. Neurological deficits and infarction area were examined. PC12 cells were exposed to oxygenglucose deprivation/reoxygenation (OGD/R) to model I/R. Expression levels of miR-187-3p and proteins related to ERS and apoptosis were measured using RT-PCR, western blotting, immunofluorescence, and immunohistochemistry, respectively. TUNEL staining was used to assay apoptosis. MCAO/R-induced morphological changes were analyzed with Nissl staining and Hematoxylin-eosin staining. I/R-induced ERS was closely associated with an increase in miR-1873p and a decrease in seipin expression. miR-187-3p agomir further activated the ERS pathway and promoted apoptosis but decreased seipin expression levels; these effects were reversed by miR-187-3p antagomir. Moreover, seipin knockdown aggravated ERS in PC12 cells after OGD/R, and this change was rescued by seipin overexpression. miR-187-3p antagomir did not suppress ERS and apoptosis in seipin knockdown PC12 cells after OGD/R. Our findings demonstrate that the inhibition of miR1873p attenuated I/Rinduced cerebral injury by regulating seipin-mediated ERS.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Traumatismo por Reperfusão
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Isquemia Encefálica
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MicroRNAs
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Estresse do Retículo Endoplasmático
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article