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

Abstract

Intracellular calcium is related to cardiac hypertrophy. The CaV1.2 channel and Ca2+/calmodulin-dependent 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 CaV1.2 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 CaV1.2 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.

• Authors: Siqi Wang, Jingyuan Li, Yan Liu, Jie Zhang, Xi Zheng, Xuefei Sun, Shuai Lei, Ze Kang, Xiye Chen, Ming Lei, Huiyuan Hu, Xiaorong Zeng, Liying Hao
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 526 Issue 4 Pg. 960-966 (06 11 2020) ISSN: 1090-2104 [Electronic] United States
• PMID: 32303334 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Cacna1c protein, rat
• Calcium Channels, L-Type
• Calmodulin
• MEF2 Transcription Factors
• MEF2C protein, rat
• Calcium-Calmodulin-Dependent Protein Kinase Type 2
• HDAC4 protein, rat
• Histone Deacetylases
• Isoproterenol

Topics

• Animals
• Calcium Channels, L-Type (metabolism)
• Calcium-Calmodulin-Dependent Protein Kinase Type 2 (metabolism)
• Calmodulin (metabolism)
• Cardiomegaly (chemically induced, metabolism, pathology)
• Disease Models, Animal
• Histone Deacetylases (metabolism)
• Isoproterenol
• MEF2 Transcription Factors (metabolism)
• Male
• Phosphorylation
• Rats, Sprague-Dawley