SERCA2a ameliorates cardiomyocyte T-tubule remodeling via the calpain/JPH2 pathway to improve cardiac function in myocardial ischemia/reperfusion mice

SERCA2a ameliorates cardiomyocyte T-tubule remodeling via the calpain/JPH2 pathway to improve cardiac function in myocardial ischemia/reperfusion mice

Abstract Transverse-tubules (T-tubules) play pivotal roles in Ca2+-induced, Ca2+ release and excitation–contraction coupling in cardiomyocytes. The purpose of this study was to uncover mechanisms where sarco/endoplasmic reticulum Ca2+ ATPase (SERCA2a) improved cardiac function through T-tubule regul...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Shuai Wang, You Zhou, Yuanyuan Luo, Rongsheng Kan, Jingwen Chen, Haochen Xuan, Chaofan Wang, Junhong Chen, Tongda Xu, Dongye Li
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2021
Materias:
Medicine
R
Science
Q
Acceso en línea:https://doaj.org/article/5aaa86db53da43a1b5b3db0e7ab7962e
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:5aaa86db53da43a1b5b3db0e7ab7962e
record_format dspace
spelling oai:doaj.org-article:5aaa86db53da43a1b5b3db0e7ab7962e2021-12-02T13:50:42ZSERCA2a ameliorates cardiomyocyte T-tubule remodeling via the calpain/JPH2 pathway to improve cardiac function in myocardial ischemia/reperfusion mice10.1038/s41598-021-81570-42045-2322https://doaj.org/article/5aaa86db53da43a1b5b3db0e7ab7962e2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81570-4https://doaj.org/toc/2045-2322Abstract Transverse-tubules (T-tubules) play pivotal roles in Ca2+-induced, Ca2+ release and excitation–contraction coupling in cardiomyocytes. The purpose of this study was to uncover mechanisms where sarco/endoplasmic reticulum Ca2+ ATPase (SERCA2a) improved cardiac function through T-tubule regulation during myocardial ischemia/reperfusion (I/R). SERCA2a protein expression, cytoplasmic [Ca2+]i, calpain activity, junctophilin-2 (JPH2) protein expression and intracellular localization, cardiomyocyte T-tubules, contractility and calcium transients in single cardiomyocytes and in vivo cardiac functions were all examined after SERCA2a knockout and overexpression, and Calpain inhibitor PD150606 (PD) pretreatment, following myocardial I/R. This comprehensive approach was adopted to clarify SERCA2a mechanisms in improving cardiac function in mice. Calpain was activated during myocardial I/R, and led to the proteolytic cleavage of JPH2. This altered the T-tubule network, the contraction function/calcium transients in cardiomyocytes and in vivo cardiac functions. During myocardial I/R, PD pretreatment upregulated JPH2 expression and restored it to its intracellular location, repaired the T-tubule network, and contraction function/calcium transients of cardiomyocytes and cardiac functions in vivo. SERCA2a suppressed calpain activity via [Ca2+]i, and ameliorated these key indices. Our results suggest that SERCA2a ameliorates cardiomyocyte T-tubule remodeling via the calpain/JPH2 pathway, thereby improving cardiac function in myocardial I/R mice.Shuai WangYou ZhouYuanyuan LuoRongsheng KanJingwen ChenHaochen XuanChaofan WangJunhong ChenTongda XuDongye LiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Shuai Wang
You Zhou
Yuanyuan Luo
Rongsheng Kan
Jingwen Chen
Haochen Xuan
Chaofan Wang
Junhong Chen
Tongda Xu
Dongye Li
SERCA2a ameliorates cardiomyocyte T-tubule remodeling via the calpain/JPH2 pathway to improve cardiac function in myocardial ischemia/reperfusion mice
description Abstract Transverse-tubules (T-tubules) play pivotal roles in Ca2+-induced, Ca2+ release and excitation–contraction coupling in cardiomyocytes. The purpose of this study was to uncover mechanisms where sarco/endoplasmic reticulum Ca2+ ATPase (SERCA2a) improved cardiac function through T-tubule regulation during myocardial ischemia/reperfusion (I/R). SERCA2a protein expression, cytoplasmic [Ca2+]i, calpain activity, junctophilin-2 (JPH2) protein expression and intracellular localization, cardiomyocyte T-tubules, contractility and calcium transients in single cardiomyocytes and in vivo cardiac functions were all examined after SERCA2a knockout and overexpression, and Calpain inhibitor PD150606 (PD) pretreatment, following myocardial I/R. This comprehensive approach was adopted to clarify SERCA2a mechanisms in improving cardiac function in mice. Calpain was activated during myocardial I/R, and led to the proteolytic cleavage of JPH2. This altered the T-tubule network, the contraction function/calcium transients in cardiomyocytes and in vivo cardiac functions. During myocardial I/R, PD pretreatment upregulated JPH2 expression and restored it to its intracellular location, repaired the T-tubule network, and contraction function/calcium transients of cardiomyocytes and cardiac functions in vivo. SERCA2a suppressed calpain activity via [Ca2+]i, and ameliorated these key indices. Our results suggest that SERCA2a ameliorates cardiomyocyte T-tubule remodeling via the calpain/JPH2 pathway, thereby improving cardiac function in myocardial I/R mice.
format article
author Shuai Wang
You Zhou
Yuanyuan Luo
Rongsheng Kan
Jingwen Chen
Haochen Xuan
Chaofan Wang
Junhong Chen
Tongda Xu
Dongye Li
author_facet Shuai Wang
You Zhou
Yuanyuan Luo
Rongsheng Kan
Jingwen Chen
Haochen Xuan
Chaofan Wang
Junhong Chen
Tongda Xu
Dongye Li
author_sort Shuai Wang
title SERCA2a ameliorates cardiomyocyte T-tubule remodeling via the calpain/JPH2 pathway to improve cardiac function in myocardial ischemia/reperfusion mice
title_short SERCA2a ameliorates cardiomyocyte T-tubule remodeling via the calpain/JPH2 pathway to improve cardiac function in myocardial ischemia/reperfusion mice
title_full SERCA2a ameliorates cardiomyocyte T-tubule remodeling via the calpain/JPH2 pathway to improve cardiac function in myocardial ischemia/reperfusion mice
title_fullStr SERCA2a ameliorates cardiomyocyte T-tubule remodeling via the calpain/JPH2 pathway to improve cardiac function in myocardial ischemia/reperfusion mice
title_full_unstemmed SERCA2a ameliorates cardiomyocyte T-tubule remodeling via the calpain/JPH2 pathway to improve cardiac function in myocardial ischemia/reperfusion mice
title_sort serca2a ameliorates cardiomyocyte t-tubule remodeling via the calpain/jph2 pathway to improve cardiac function in myocardial ischemia/reperfusion mice
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/5aaa86db53da43a1b5b3db0e7ab7962e
work_keys_str_mv AT shuaiwang serca2aamelioratescardiomyocytettubuleremodelingviathecalpainjph2pathwaytoimprovecardiacfunctioninmyocardialischemiareperfusionmice
AT youzhou serca2aamelioratescardiomyocytettubuleremodelingviathecalpainjph2pathwaytoimprovecardiacfunctioninmyocardialischemiareperfusionmice
AT yuanyuanluo serca2aamelioratescardiomyocytettubuleremodelingviathecalpainjph2pathwaytoimprovecardiacfunctioninmyocardialischemiareperfusionmice
AT rongshengkan serca2aamelioratescardiomyocytettubuleremodelingviathecalpainjph2pathwaytoimprovecardiacfunctioninmyocardialischemiareperfusionmice
AT jingwenchen serca2aamelioratescardiomyocytettubuleremodelingviathecalpainjph2pathwaytoimprovecardiacfunctioninmyocardialischemiareperfusionmice
AT haochenxuan serca2aamelioratescardiomyocytettubuleremodelingviathecalpainjph2pathwaytoimprovecardiacfunctioninmyocardialischemiareperfusionmice
AT chaofanwang serca2aamelioratescardiomyocytettubuleremodelingviathecalpainjph2pathwaytoimprovecardiacfunctioninmyocardialischemiareperfusionmice
AT junhongchen serca2aamelioratescardiomyocytettubuleremodelingviathecalpainjph2pathwaytoimprovecardiacfunctioninmyocardialischemiareperfusionmice
AT tongdaxu serca2aamelioratescardiomyocytettubuleremodelingviathecalpainjph2pathwaytoimprovecardiacfunctioninmyocardialischemiareperfusionmice
AT dongyeli serca2aamelioratescardiomyocytettubuleremodelingviathecalpainjph2pathwaytoimprovecardiacfunctioninmyocardialischemiareperfusionmice
_version_ 1718392437972402176

Ejemplares similares