Distinct roles of calmodulin and Ca2+/calmodulin-dependent protein kinase II in isopreterenol-induced cardiac hypertrophy

被引：10

作者：

Wang, Siqi ^{[1
]}

Li, Jingyuan ^{[1
]}

Liu, Yan ^{[1
]}

Zhang, Jie ^{[1
]}

Zheng, Xi ^{[1
]}

Sun, Xuefei ^{[1
]}

Lei, Shuai ^{[1
]}

Kang, Ze ^{[1
]}

Chen, Xiye ^{[1
]}

Lei, Ming ^{[2
]}

Hu, Huiyuan ^{[1
]}

Zeng, Xiaorong ^{[2
]}

Hao, Liying ^{[1
]}

机构：

[1] China Med Univ, Sch Pharm, Dept Pharmaceut Toxicol, 77 Puhe Rd, Shenyang 110122, Peoples R China

[2] Southwest Med Univ, Collaborat Innovat Ctr Prevent & Treatment Cardio, Inst Cardiovasc Res, Key Lab Med Electrophysiol,Minist Educ, 319 Zhongshan Rd, Luzhou 646000, Sichuan, Peoples R China

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2020年 / 526卷 / 04期

基金：

中国国家自然科学基金;

关键词：

Cardiac hypertrophy; Ca(v)1.2; Ca2+/calmodulin-dependent protein kinase II; Calmodulin; CAMKII-DEPENDENT PHOSPHORYLATION; INACTIVATION; ACTIVATION;

D O I：

10.1016/j.bbrc.2020.03.188

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Intracellular calcium is related to cardiac hypertrophy. The Ca(v)1.2 channel and Ca2+/calmodulindependent protein kinase II (CaMKII) and CaM regulate the intracellular calcium content. However, the differences in CaMKII and CaM in cardiac hypertrophy are still conflicting and are worthy of studying as drug targets. Therefore, in this study, we aim to investigate the roles and mechanism of CaM and CaMKII on Ca(v)1.2 in pathological myocardial hypertrophy. The results showed that ISO stimulation caused SD rat heart and cardiomyocyte hypertrophy. In vivo, the HW/BW, LVW/BW, cross-sectional area, fibrosis ratio and ANP expression were all increased. There were no differences in Ca(v)1.2 channel expression in the in vivo model or the in vitro model, but the ISO stimulation induced channel activity, and the [Ca2+](i) increased. The protein expression levels of CaMKII and p-CaMKII were all increased in the ISO group, but the CaM expression level decreased. AIP inhibited ANP, CaMKII and p-CaMKII expression, and ISO-induced [Ca2+](i) increased. AIP also reduced HDAC4, p-HDAC and MEF2C expression. However, CMZ did not play a cardiac hypertrophy reversal role in vitro. In conclusion, we considered that compared with CaM, CaMKII may be a much more important drug target in cardiac hypertrophy reversal. (C) 2020 Elsevier Inc. All rights reserved.

引用

页码：960 / 966

页数：7

共 28 条

[21] NADPH oxidase 2 mediates angiotensin II-dependent cellular arrhythmias via PKA and CaMKII [J].