LRP6-mediated phosphorylation of connexin43 in myocardial infarction

Summary: Ventricular tachycardia (VT) and ventricular fibrillation are most causes of early death in patients with acute myocardial infarction (AMI). Conditional cardiac-specific low-density lipoprotein receptor-related protein 6 (LRP6)-knockout mice with connexin 43 (Cx43) reduction triggered the l...

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Main Authors: Xu-min Zhang, Ya-ling Liu, Ying Cai, Ying Hao, Sheng Kang
Format: Article
Language:English
Published: Elsevier 2023-03-01
Series:iScience
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004223002377
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author Xu-min Zhang
Ya-ling Liu
Ying Cai
Ying Hao
Sheng Kang
author_facet Xu-min Zhang
Ya-ling Liu
Ying Cai
Ying Hao
Sheng Kang
author_sort Xu-min Zhang
collection DOAJ
description Summary: Ventricular tachycardia (VT) and ventricular fibrillation are most causes of early death in patients with acute myocardial infarction (AMI). Conditional cardiac-specific low-density lipoprotein receptor-related protein 6 (LRP6)-knockout mice with connexin 43 (Cx43) reduction triggered the lethal ventricular arrhythmias. Thus, it is necessary for exploring whether LRP6 and its upstream genes circRNA1615 mediate the phosphorylation of Cx43 in VT of AMI. Here, we showed that circRNA1615 regulated the expression of LRP6 mRNA through sponge adsorption of miR-152-3p. Importantly, LRP6 interference fragments aggravated hypoxia injury of Cx43, while overexpression of LRP6 improved the phosphorylation of Cx43. Subsequently, interference with G-protein alpha subunit (Gαs) downstream of LRP6 further inhibited the phosphorylation of Cx43, along with increasing VT. Our results demonstrated that LRP6 upstream genes circRNA1615 controlled the damage effect and VT in AMI, and LRP6 mediated the phosphorylation of Cx43 via Gαs which played a role in VT of AMI.
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spelling doaj.art-df5b5b0edd074061a5430780e6c6cb842023-02-26T04:27:44ZengElsevieriScience2589-00422023-03-01263106160LRP6-mediated phosphorylation of connexin43 in myocardial infarctionXu-min Zhang0Ya-ling Liu1Ying Cai2Ying Hao3Sheng Kang4Department of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, Jimo Road 150, Shanghai 200120, ChinaDepartment of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Pujian Road 160, Shanghai 200127, ChinaDepartment of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, Jimo Road 150, Shanghai 200120, ChinaDepartment of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, Jimo Road 150, Shanghai 200120, ChinaDepartment of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, Jimo Road 150, Shanghai 200120, China; Corresponding authorSummary: Ventricular tachycardia (VT) and ventricular fibrillation are most causes of early death in patients with acute myocardial infarction (AMI). Conditional cardiac-specific low-density lipoprotein receptor-related protein 6 (LRP6)-knockout mice with connexin 43 (Cx43) reduction triggered the lethal ventricular arrhythmias. Thus, it is necessary for exploring whether LRP6 and its upstream genes circRNA1615 mediate the phosphorylation of Cx43 in VT of AMI. Here, we showed that circRNA1615 regulated the expression of LRP6 mRNA through sponge adsorption of miR-152-3p. Importantly, LRP6 interference fragments aggravated hypoxia injury of Cx43, while overexpression of LRP6 improved the phosphorylation of Cx43. Subsequently, interference with G-protein alpha subunit (Gαs) downstream of LRP6 further inhibited the phosphorylation of Cx43, along with increasing VT. Our results demonstrated that LRP6 upstream genes circRNA1615 controlled the damage effect and VT in AMI, and LRP6 mediated the phosphorylation of Cx43 via Gαs which played a role in VT of AMI.http://www.sciencedirect.com/science/article/pii/S2589004223002377Biological sciencesBiochemistryMolecular biologyCell biology
spellingShingle Xu-min Zhang
Ya-ling Liu
Ying Cai
Ying Hao
Sheng Kang
LRP6-mediated phosphorylation of connexin43 in myocardial infarction
iScience
Biological sciences
Biochemistry
Molecular biology
Cell biology
title LRP6-mediated phosphorylation of connexin43 in myocardial infarction
title_full LRP6-mediated phosphorylation of connexin43 in myocardial infarction
title_fullStr LRP6-mediated phosphorylation of connexin43 in myocardial infarction
title_full_unstemmed LRP6-mediated phosphorylation of connexin43 in myocardial infarction
title_short LRP6-mediated phosphorylation of connexin43 in myocardial infarction
title_sort lrp6 mediated phosphorylation of connexin43 in myocardial infarction
topic Biological sciences
Biochemistry
Molecular biology
Cell biology
url http://www.sciencedirect.com/science/article/pii/S2589004223002377
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