P38 MAPK/miR-1 are involved in the protective effect of EGCG in high glucose-induced Cx43 downregulation in neonatal rat cardiomyocytes.
The remodeling of cardiac gap junctions contributes to various arrhythmias in a diabetic heart. We previously reported that Epigallocatechin-3-gallate (EGCG) attenuated connexin43 (Cx43) protein downregulation induced by high glucose (HG) in neonatal rat cardiomyocytes, but Cx43 mRNA expression was not affected. It indicated the possible mechanisms of post-transcriptional regulation, which still remains unclear. As microRNAs (miRNAs) regulate gene expression widely at post-transcriptional level, we measured miR-1/206 in cardiomyocytes treated with HG and EGCG by quantitative RT-PCR and investigated their relationship with signal transduction pathways. The results showed that HG induced miR-1/206 elevation by PKC MAPK pathway. Moreover, we tested the negative regulation effect of miR-1/206 on Cx43 protein by miRNAs transfection. EGCG, however, nearly abolished the HG-induced miR-1 augmentation via P38 MAPK pathway. Therefore, our study suggested that PKC-activated miR-1/206 expression might contribute to Cx43 downregulation in HG-treated cardiomyocytes, and EGCG conferred protective effect by inhibiting miR-1 elevation via P38 MAPK pathway.
Department of Cardiovascular Medicine, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou, Zhejiang, 310016, China.
Lu
L
Yu
Department of Cardiovascular Medicine, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou, Zhejiang, 310016, China.
Hongmei
H
Yu
Department of Cardiovascular Medicine, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou, Zhejiang, 310016, China.
Xiaoting
X
Li
Department of Cardiovascular Medicine, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou, Zhejiang, 310016, China.
Chongying
C
Jin
Department of Cardiovascular Medicine, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou, Zhejiang, 310016, China.
Yanbo
Y
Zhao
Department of Cardiovascular Medicine, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou, Zhejiang, 310016, China.
Shengjie
S
Xu
Department of Cardiovascular Medicine, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, 3 East Qingchun Road, Hangzhou, Zhejiang, 310016, China.
Xia
X
Sheng
D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D018031:Connexin 43 / Q000378:metabolism*; D015536:Down-Regulation; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D035683:MicroRNAs / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D018031:Connexin 43; C542191:MIRN1 microRNA, rat; D035683:MicroRNAs; D002392:Catechin; C045651:epigallocatechin gallate; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose
MicroRNA; cardiomyocytes; connexin43; high glucose