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Role of selenoprotein M knockdown in the melatonin antagonism of nickel-induced apoptosis and endoplasmic reticulum stress in mouse heart

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2023年第5期24卷 406-417页

作者： Xintong ZHANG Xiaoxue GAI Lihua XU Wenxue MA Qiaohan LIU Bendong SHI Cheng FANG Jingzeng CAI Ziwei ZHANG College of Veterinary Medicine Northeast Agricultural UniversityHarbin 150030China Suihua Agricultural and Rural Bureau Suihua 152000China College of Veterinary Medicine Northeast Agricultural UniversityHarbin 150030China4.Key Laboratory of the Provincial EducationDepartment of Heilongjiang for Common Animal Disease Prevention and TreatmentNortheast Agricultural UniversityHarbin 150030China

The aim of this study was to investigate the role of selenoprotein M(SelM)in endoplasmic reticulum stress and apoptosis in nickel-exposed mouse hearts and to explore the detoxifying effects of melatonin.At 21 d after intraperitoneal injection of nickel chloride(NiCl_(2))and/or melatonin into male wild-type(WT)and SelM knockout(KO)C57BL/6J mice,NiCl_(2)was found to induce changes in the microstructure and ultrastructure of the hearts of both WT and SelM KO mice,which were caused by oxidative stress,endoplasmic reticulum stress,and apoptosis,as evidenced by decreases in malondialdehyde(MDA)content and total antioxidant capacity(T-AOC)activity.Changes in the messenger RNA(mRNA)and protein expression of genes related to endoplasmic reticulum stress(activating transcription factor 4(ATF4),inositol-requiring protein 1(IRE1),c-Jun N-terminal kinase(JNK),and C/EBP homologous protein(CHOP))and apoptosis(B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),Caspase-3,Caspase-9,and Caspase-12)were also observed.Notably,the observed damage was worse in SelM KO mice.Furthermore,melatonin alleviated the heart injury caused by NiCl_(2)in WT mice but could not exert a good protective effect in the heart of SelM KO mice.Overall,the findings suggested that the antioxidant capacity of SelM,as well as its modulation of endoplasmic reticulum stress and apoptosis,plays important roles in nickel-induced heart injury.

关键词： Selenoprotein M(SelM) Nickel chloride(NiCl_(2)) Melatonin Apoptosis mouse heart

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