title: Protein kinase Cα inhibits myocardin-induced cardiomyocyte hypertrophy through the promotion of myocardin phosphorylation.
abstract: Myocardin plays a key role in the development of cardiac hypertrophy. However, the upstream signals that control the stability and transactivity of myocardin remain to be fully understood. The expression of protein kinase Cα (PKCα) also induces cardiac hypertrophy. An essential downstream molecule of PKCα, extracellular signal-regulated kinase 1/2, was reported to negatively regulate the activities of myocardin. But, the effect of cooperation between PKCα and myocardin and the potential molecular mechanism by which PKCα regulates myocardin-mediated cardiac hypertrophy are unclear. In this study, a luciferase assay was performed using H9C2 cells transfected with expression plasmids for PKCα and myocardin. Surprisingly, the results showed that PKCα inhibited the transcriptional activity of myocardin. PKCα inhibited myocardin-induced cardiomyocyte hypertrophy, demonstrated by the decrease in cell surface area and fetal gene expression, in cardiomyocyte cells overexpressing PKCα and myocardin. The potential mechanism underlying the inhibition effect of PKCα on the function of myocardin is further explored. PKCα directly promoted the basal phosphorylation of endogenous myocardin at serine and threonine residues. In myocardin-overexpressing cardiomyocyte cells, PKCα induced the excessive phosphorylation of myocardin, resulting in the degradation of myocardin and a transcriptional suppression of hypertrophic genes. These results demonstrated that PKCα inhibits myocardin-induced cardiomyocyte hypertrophy through the promotion of myocardin phosphorylation.
authors.affiliation: Key Laboratory of Industrial Microbiology, Ministry of Education and Tianjin City, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China.
authors.forename: Weizong
authors.initials: W
authors.lastname: Li
authors.affiliation: Key Laboratory of Industrial Microbiology, Ministry of Education and Tianjin City, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China tony@tust.edu.cn wn929@tust.edu.cn.
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.affiliation: Key Laboratory of Industrial Microbiology, Ministry of Education and Tianjin City, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China.
authors.forename: Man
authors.initials: M
authors.lastname: Li
authors.affiliation: Key Laboratory of Industrial Microbiology, Ministry of Education and Tianjin City, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China.
authors.forename: Huiqin
authors.initials: H
authors.lastname: Gong
authors.affiliation: Key Laboratory of Industrial Microbiology, Ministry of Education and Tianjin City, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China Department of Biochemistry, Medical College, Wuhan University of Science and Technology, Wuhan 430081, China.
authors.forename: Xinghua
authors.initials: X
authors.lastname: Liao
authors.affiliation: Key Laboratory of Industrial Microbiology, Ministry of Education and Tianjin City, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Yang
authors.affiliation: Key Laboratory of Industrial Microbiology, Ministry of Education and Tianjin City, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China Department of Biochemistry, Medical College, Wuhan University of Science and Technology, Wuhan 430081, China tony@tust.edu.cn wn929@tust.edu.cn.
authors.forename: Tongcun
authors.initials: T
authors.lastname: Zhang
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000473:pathology*; D002460:Cell Line; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000502:physiology*; D010766:Phosphorylation; D051571:Protein Kinase C-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D059748:Proteolysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015534:Trans-Activators / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology; D000099251:Myocardin
chemical_list: D009687:Nuclear Proteins; D051571:Protein Kinase C-alpha; D047428:Protein Kinase Inhibitors; D015534:Trans-Activators; D000099251:Myocardin
keywords: PKCα; cardiomyocyte hypertrophy; myocardin; phosphorylation