Role of GRP75 and VDAC1 in heroin-induced arrhythmia
10.12007/j.issn.0258-4646.2025.08.009
- VernacularTitle:GRP75和VDAC1在海洛因致心律失常中的作用
- Author:
Yaling GUAN
1
;
Liping SU
;
Li LIU
;
Min JI
;
Mengjie ZHUANG
;
Sensen ZHU
;
Hongwei PU
Author Information
1. 新疆第二医学院细胞生物学与遗传学教研室,新疆克拉玛依 834000
- Publication Type:Journal Article
- Keywords:
heroin;
arrhythmia;
glucose-regulated protein 75;
voltage-dependent anion channel 1
- From:
Journal of China Medical University
2025;54(8):720-726
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the roles of glucose-regulated protein 75(GRP75)and voltage-dependent anion channel 1(VDAC1)in heroin-induced arrhythmia.Methods Based on transcriptomic data from primary myocardial cells treated with heroin and the GSE31821 dataset from the Gene Expression Omnibus(GEO),differentially expressed genes(DEGs)were identified using R software.Enrichment analysis of DEGs was performed.The protein-protein interaction(PPI)network was constructed using STRING database,and key genes were selected using Cytoscape.Molecular docking of key genes was performed using HDOCK,followed by in vivo valida-tion.A total of 60 SD rats were randomly divided into control,model,model+7 d,model+14 d,and model+21 d groups.A rat model of heroin addiction was established,and the expression levels of DEGs in myocardial tissue were assessed using immunohistochemical staining and quantitative real-time PCR.Results A total of 51 DEGs primarily enriched in muscle cell development,myofibrils,actin binding,arrhythmic right ventricular cardiomyopathy,calcium signaling,and apoptosis pathways were identified.Based on the PPI and Cytoscape analyses,GRP75 and VDAC1 were identified as key genes.Molecular docking indicated a strong interaction between GRP75 and VDAC1,which form a stable complex.The results of immunohistochemical staining and qRT-PCR showed that the expression levels of GRP75 and VDAC1 were significantly increased in the model group compared to those in the control group(P＜0.05),and their expres-sion increased(P＜0.05)with the intervention period of heroin in a time-dependent manner.Conclusion GRP75 and VDAC1 may con-tribute to heroin-induced arrhythmogenesis.
