Volume 30, Issue 2, 2021
DOI: 10.24205/03276716.2020.4090
MICAL3 AFFECTS MYOCARDIAL HYPERTROPHY BY REGULATING CK2?1/HDAC2 PATHWAY
Abstract
OBJECTIVE: In order to study the role and mechanism of MICAL3 in Ang II-induced myocardial hypertrophy, with cardiomyocyte H9C2 as the focus, the paper established a model of Ang II-induced myocardial hypertrophic cells, and profoundly explored the role of MICAL3 in myocardial hypertrophy and the molecular mechanism.
Methods: The constructed expression plasmid of MICAL3 gene and the Control plasmid were transfected into H9C2 cells. Ang II stimulation was performed. Immunofluorescence technique was used to detect the degree of hypertrophy of H9C2 cells. Fluorescent probes and microplate reader were employed to detect the level of ROS in cardiomyocytes and the HDAC2 activity. Western blot method was applied to detect the phosphorylation level of HDAC. Immunoprecipitation was used to detect the effect of MICAL3 on the interaction between CK2?1 and HDAC2.
Results: The overexpression of MICAL3 protein can block the hypertrophy of cardiomyocytes caused by Ang II, and significantly increase the level of ROS in cardiomyocytes while reducing HDAC2 activity. MICAL3 can compete with HDAC2 and affect the interaction between HDAC2 and CK2?1, thereby reducing the phosphorylation level of HDAC2 at S394 site.
Conclusion: MICAL3 can negatively regulate the hypertrophy of cardiomyocytes caused by Ang II. On the one hand, MICAL3 can competitively inhibit the interaction between HDAC2 and CK2?1, reduce the phosphorylation level of HDAC2 at S394 site and inhibit the activity of HDAC2. On the other hand, MICAL3 inhibits the activity of HDAC2 through the self-generated ROS, thereby inhibiting the HDAC2 positive regulation of myocardial hypertrophy and inhibiting the hypertrophy of myocardial cells.
Keywords
MICAL3; Myocardial Hypertrophy; Ang II; CK2?1/HDAC2