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GPR43 protects human A16 cardiomyocytes against hypoxia/reoxygenation injury by regulating nesfatin1
Affiliations- Cardiovascular Care Unit, The First Hospital of Hebei Medical University, Shijiazhuang, China
open access
Abstract
Background: The purpose of this study is to investigate the regulatory role of G coupled-protein receptor 43 (GPR43) during myocardial ischemia/reperfusion (I/R) injury and to explore the relevant molecular mechanism.
Materials and methods: AC16 hypoxia/reoxygenation (H/R) model was established to simulate I/R injury in vitro. Gain- and loss-of-function experiments were conducted to regulate GPR43 or nesfatin1 expression. Cell viability and apoptosis was examined adopting CCK-8 and TUNEL assays. Commercial kits were applied for detecting ROS and inflammatory cytokines. Quantitative real-time PCR (qRT-PCR) and western blotting were conducted to measure the expression level of critical genes and proteins.
Results: GPR43 was downregulated in H/R-mediated AC16 cells. GPR43 overexpression or the GPR43 agonist greatly inhibited H/R-induced cell viability loss, cell apoptosis, and excessive production of ROS and pro-inflammatory cytokines in AC16 cardiomyocytes. Co-immunoprecipitation (Co-IP) assay identified an interaction between GPR43 and nesfatin1, and GPR43 could positively regulate nesfatin1. In addition, the protective role of GPR43 against H/R injury was partly abolished upon nesfatin1 knockdown. Eventually, GPR43 could inhibit H/R-stimulated JNK/P38 MAPK signaling in AC16 cells, which was also hindered by nesfatin1 knockdown.
Conclusions: Our findings demonstrated the protective role of GPR43 against H/R-mediated cardiomyocytes injury through up-regulating nesfatin1, providing a novel target for the prevention and treatment of myocardial I/R injury.
Abstract
Background: The purpose of this study is to investigate the regulatory role of G coupled-protein receptor 43 (GPR43) during myocardial ischemia/reperfusion (I/R) injury and to explore the relevant molecular mechanism.
Materials and methods: AC16 hypoxia/reoxygenation (H/R) model was established to simulate I/R injury in vitro. Gain- and loss-of-function experiments were conducted to regulate GPR43 or nesfatin1 expression. Cell viability and apoptosis was examined adopting CCK-8 and TUNEL assays. Commercial kits were applied for detecting ROS and inflammatory cytokines. Quantitative real-time PCR (qRT-PCR) and western blotting were conducted to measure the expression level of critical genes and proteins.
Results: GPR43 was downregulated in H/R-mediated AC16 cells. GPR43 overexpression or the GPR43 agonist greatly inhibited H/R-induced cell viability loss, cell apoptosis, and excessive production of ROS and pro-inflammatory cytokines in AC16 cardiomyocytes. Co-immunoprecipitation (Co-IP) assay identified an interaction between GPR43 and nesfatin1, and GPR43 could positively regulate nesfatin1. In addition, the protective role of GPR43 against H/R injury was partly abolished upon nesfatin1 knockdown. Eventually, GPR43 could inhibit H/R-stimulated JNK/P38 MAPK signaling in AC16 cells, which was also hindered by nesfatin1 knockdown.
Conclusions: Our findings demonstrated the protective role of GPR43 against H/R-mediated cardiomyocytes injury through up-regulating nesfatin1, providing a novel target for the prevention and treatment of myocardial I/R injury.
Keywords
hypoxia/reoxygenation, cardiomyocyte, GPR43, nesfatin1
About this articleTitle
GPR43 protects human A16 cardiomyocytes against hypoxia/reoxygenation injury by regulating nesfatin1
Journal
Issue
Article type
Original article
Published online
2023-06-05
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414
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262
DOI
Pubmed
Keywords
hypoxia/reoxygenation
cardiomyocyte
GPR43
nesfatin1
Authors
Jie Yu
Qingquan Li
Chang Guan
Ming Yuan
Ding Yu
Yaqin Wang
Mengyao Liu
Ying Lv
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