Effect and mechanism of miR-34a-5p targeting Notch1 on H/R-induced apoptosis of human cardiomyocytes
10.19405/j.cnki.issn1000-1492.2024.05.011
- VernacularTitle:miR-34a-5p靶向Notch1对H/R诱导的人心肌细胞凋亡的影响及机制
- Author:
Longzhen LIU
1
;
Liang HONG
;
Bing SONG
Author Information
1. 安徽医科大学第一附属医院心内科,合肥 230022
- Keywords:
hypoxia/reoxygenation;
endoplasmic reticulum stress;
myocardial cells;
miR-34a-5p;
Notch1
- From:
Acta Universitatis Medicinalis Anhui
2024;59(5):815-820
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the improvement of endoplasmic reticulum stress mediated by microRNA (miR)-34a-5p/transmembrane fusion protein 1(Notch1) signaling axis on hypoxia/reoxygenation (H/R) human cardiomyocytes.Methods Human cardiomyocytes were randomly divided into Control group, H/R group, mimic NC group, mimic group, inhibitor NC group and inhibitor group.Except the Control group, H/R injury model was established in other groups.The expression levels of miR-34a-5p and Notch1 were detected by quantitative real-time polymerase chain reaction (qRT-PCR) , cell survival rate was detected by thiazolyl blue (MTT) , cell apopto-sis rate was detected by flow cytometry, and the targeting relationship between miR-34a-5p and Notch1 was detec-ted by dual luciferase gene reporting method.The expressions of transcriptional activator 6 (ATF6), inositol demand enzyme 1 (IRE 1), protein kinase - like endoplasmic reticulum kinase (PERK) and glucose regulatory protein 78 (GRP78) were detected by Western blot.Results miR-34a-5p targeted Notch1 (P<0.05); compared with Con-trol group, the expression level of miR-34a-5p, apoptosis rate and protein expressions of ATF6, IRE1, PERK and GRP78 in H/R group increased, while the cell survival rate and Notch1 mRNA and protein expressions decreased (P<0.05).Compared with H/R group and mimic NC group, miR-34a-5p expression, apoptosis rate, and protein expressions of ATF6, IRE1, PERK and GRP78 in mimic group increased, while cell survival rate and Notch1 mR-NA and protein expressions decreased (P<0.05).Compared with H/R group and inhibitor NC group, the expres-sion of miR-34a-5p, apoptosis rate and protein expressions of ATF6, IRE1, PERK and GRP78 decreased in inhibi-tor group, while cell survival rate and Notch1 mRNA and protein expressions increased (P<0.05).Conclusion miR-34a-5p can inhibit the apoptosis of H/R human cardiomyocytes, possibly through the targeted inhibition of Notch1-mediated endoplasmic reticulum stress.
- Full text:2024072815184251391miR-34a-5p靶向N...人心肌细胞凋亡的影响及机制_刘龙珍.pdf
