中国药理学通报2024，Vol.40Issue(8)：1437-1446,10.DOI:10.12360/CPB202404043
LncRNA-CCRR通过调控UBA6影响钠通道泛素化进而调控心梗后心律失常
LncRNA-CCRR regulates arrhythmia induced by myocardial infarction by affecting sodium channel ubiquitination via UBA6
摘要
Abstract
Aim To investigate the regulatory mecha-nism of arrhythmia of sodium channel ubiquitination af-ter MI and to study the electrophysiological remodeling mechanism of lncRNA-CCRR after MI for the preven-tion and treatment of arrhythmia after MI.Methods LncRNA-CCRR transgenic mice and C57BL/6 mice injected with lncRNA-CCRR overexpressed adeno-asso-ciated virus were used.Four weeks after infection,the left anterior descending branch of the coronary artery was ligated for 12 h to establish a mouse acute myocar-dial infarction model,and the incidence of arrhythmia was detected by programmed electrical stimulation.Ln-cRNA-CCRR overexpression/knockdown adeno-associ-ated virus and negative control were transfected into neonatal mouse cardiomyocytes(NMCMs),and the model was prepared by hypoxia for 12 h.LncRNA-CCRR expression was detected by FISH,Nav1.5 and UBA6 protein and Nav.1.5 mRNA expression were de-tected by Western blot and real-time quantitative poly-merase chain reaction(qRT-PCR),Nav1.5 and UBA6 expressions were detected by immunofluores-cence,and the relationship between lncRNA-CCRR and UBA6 was detected by RIP.INa current density af-ter CCRR overexpression and knockdown was detected by Whole-cell clamp patch.Results In MI mice,the expression of lncRNA-CCRR decreased,the incidence of arrhythmia increased,the expression of CCRR and Nav1.5 mRNA was down-regulated,the protein ex-pression of Nav1.5 was down-regulated,and the pro-tein expression of UBA6 was up-regulated compared with sham group.Overexpression of CCRR could re-verse the above changes.AAV-CCRR could reverse the down-regulated CCRR and Nav1.5 mRNA levels af-ter hypoxia,and improve the expression of Nav1.5 and UBA6 protein.The direct relationship between ln-cRNA-CCRR and UBA6 was identified by RIP analy-sis.The INa density increased after transfection with AAV-CCRR.The INa density decreased after transfec-tion with AAV-si-CCRR.Conclusions The expres-sion of lncRNA-CCRR decreases after MI,and ln-cRNA-CCRR can improve arrhythmia induced by MI by inhibiting UBA6 to increase the protein expression level of Nav1.5 and the density of INa.关键词
心肌梗死/lncRNA-CCRR/UBA6/钠通道/泛素化/心律失常Key words
myocardial infarction/lncRNA-CCRR/UBA6/sodium channel/ubiquitination/arrhythmia分类
医药卫生引用本文复制引用
孙飞涵,李聃宁,杨华,王圣洁,罗惠珊,郭建军,宣立娜,孙丽华..LncRNA-CCRR通过调控UBA6影响钠通道泛素化进而调控心梗后心律失常[J].中国药理学通报,2024,40(8):1437-1446,10.基金项目
黑龙江省自然科学基金资助项目(No LH2022H002) （No LH2022H002）
