中国药理学通报2023，Vol.39Issue(12)：2258-2265,8.DOI:10.12360/CPB202303001
甲基化转移酶样蛋白3介导的m6A修饰参与高静水压诱导的心房肌细胞电重塑
METTL3-mediated m6A modification involved in electrical remodeling of atrial cardiomyocytes under high hydrostatic pressure
摘要
Abstract
Aim To investigate the regulation of N6-methyladenosine(m6A)modification on L-type calci-um channels in atrial myocytes under high hydrostatic pressure,mediated by methyltransferase-like protein 3(METTL3).Methods C57BL/6J mice were ran-domly assigned to the control group and the hyperten-sion group(treated with continuous administration of angiotensin for four weeks).Masson staining was used to observe the fibrosis of mouse atrial tissue,while dot blot assay and Western blot were used to detect the lev-els of m6A,METTL3,and Cav1.2 in the atrial tissue.A high hydrostatic pressure model was constructed u-sing the HL-1 cell line cultured in vitro,and METTL3 was intervened to observe changes in m6A expression levels,METTL3 and Cav1.2 levels in cells,and action potential duration(APD)and L-type calcium current(ICa,L)were detected using whole-cell patch clamp.Results Compared to the control group,the hyperten-sion group showed disordered atrial myocyte morpholo-gy,increased interstitial fibrosis,significant increased m6A content and METTL3 expression levels in the atri-al tissue,and decreased expression of ion channel pro-tein Cav1.2.In HL-1 cells cultured in vitro,increasing hydrostatic pressure(0,20,40 mmHg)up-regulated m6 A and METTL3 expression levels,down-regulated Cav1.2,and these changes were reversed with STM2457 and si-METTL3.Furthermore,specific MET-TL3 inhibitor STM2457 reversed the shortening of APD and the decrease of ICa L peak density in HL-1 cells caused by high hydrostatic pressure,while METTL3 di-rectly bound to CACNA1C.Conclusion METTL3-mediated m6A modification might directly regulate CACNA1C to participate in electrical remodeling of at-rial myocytes under high hydrostatic pressure.关键词
METTL3/高静水压/m6A/L型钙通道/心房电重塑/房颤Key words
METTL3/high hydrostatic pressure/m6A/L-type calcium channel/atrial electrical remod-eling/atrial fibrillation分类
医药卫生引用本文复制引用
刘攀月,魏薇,曾珑,肖海茵,肖菲菲,朱蕊,杨慧,邝素娟,邓春玉,饶芳..甲基化转移酶样蛋白3介导的m6A修饰参与高静水压诱导的心房肌细胞电重塑[J].中国药理学通报,2023,39(12):2258-2265,8.基金项目
国家自然科学基金青年科学基金项目(No 81900301) （No 81900301）
