The purified extract of steamed Panax ginseng protects cardiomyocyte from ischemic injury via caveolin-1 phosphorylation-mediating calcium influx

Background: Caveolin-1, the scaffolding protein of cholesterol-rich invaginations, plays an important role in store-operated Ca2+ influx and its phosphorylation at Tyr14 (p-caveolin-1) is vital to mobilize protection against myocardial ischemia (MI) injury. SOCE, comprising STIM1, ORAI1 and TRPC1, c...

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Main Authors: Hai-Xia Li, Yan Ma, Yu-Xiao Yan, Xin-Ke Zhai, Meng-Yu Xin, Tian Wang, Dong-Cao Xu, Yu-Tong Song, Chun-Dong Song, Cheng-Xue Pan
Format: Article
Language:English
Published: Elsevier 2023-11-01
Series:Journal of Ginseng Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1226845323000775
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author Hai-Xia Li
Yan Ma
Yu-Xiao Yan
Xin-Ke Zhai
Meng-Yu Xin
Tian Wang
Dong-Cao Xu
Yu-Tong Song
Chun-Dong Song
Cheng-Xue Pan
author_facet Hai-Xia Li
Yan Ma
Yu-Xiao Yan
Xin-Ke Zhai
Meng-Yu Xin
Tian Wang
Dong-Cao Xu
Yu-Tong Song
Chun-Dong Song
Cheng-Xue Pan
author_sort Hai-Xia Li
collection DOAJ
description Background: Caveolin-1, the scaffolding protein of cholesterol-rich invaginations, plays an important role in store-operated Ca2+ influx and its phosphorylation at Tyr14 (p-caveolin-1) is vital to mobilize protection against myocardial ischemia (MI) injury. SOCE, comprising STIM1, ORAI1 and TRPC1, contributes to intracellular Ca2+ ([Ca2+]i) accumulation in cardiomyocytes. The purified extract of steamed Panax ginseng (EPG) attenuated [Ca2+]i overload against MI injury. Thus, the aim of this study was to investigate the possibility of EPG affecting p-caveolin-1 to further mediate SOCE/[Ca2+]i against MI injury in neonatal rat cardiomyocytes and a rat model. Methods: PP2, an inhibitor of p-caveolin-1, was used. Cell viability, [Ca2+]i concentration were analyzed in cardiomyocytes. In rats, myocardial infarct size, pathological damages, apoptosis and cardiac fibrosis were evaluated, p-caveolin-1 and STIM1 were detected by immunofluorescence, and the levels of caveolin-1, STIM1, ORAI1 and TRPC1 were determined by RT-PCR and Western blot. And, release of LDH, cTnI and BNP was measured. Results: EPG, ginsenosides accounting for 57.96%, suppressed release of LDH, cTnI and BNP, and protected cardiomyocytes by inhibiting Ca2+ influx. And, EPG significantly relieved myocardial infarct size, cardiac apoptosis, fibrosis, and ultrastructure abnormality. Moreover, EPG negatively regulated SOCE via increasing p-caveolin-1 protein, decreasing ORAI1 mRNA and protein levels of ORAI1, TRPC1 and STIM1. More importantly, inhibition of the p-caveolin-1 significantly suppressed all of the above cardioprotection of EPG. Conclusions: Caveolin-1 phosphorylation is involved in the protective effects of EPG against MI injury via increasing p-caveolin-1 to negatively regulate SOCE/[Ca2+]i.
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spelling doaj.art-89a210ecd96d40b99360c9c8c738158a2023-11-18T04:28:18ZengElsevierJournal of Ginseng Research1226-84532023-11-01476755765The purified extract of steamed Panax ginseng protects cardiomyocyte from ischemic injury via caveolin-1 phosphorylation-mediating calcium influxHai-Xia Li0Yan Ma1Yu-Xiao Yan2Xin-Ke Zhai3Meng-Yu Xin4Tian Wang5Dong-Cao Xu6Yu-Tong Song7Chun-Dong Song8Cheng-Xue Pan9School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan Province, China; Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou, Henan Province, ChinaSchool of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan Province, ChinaSchool of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan Province, ChinaSchool of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan Province, ChinaSchool of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan Province, ChinaSchool of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan Province, ChinaSchool of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan Province, ChinaSchool of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan Province, ChinaThe First Affiliated Hospital of Henan University of Traditional Chinese Medicine, 9 Renmin Road, Zhengzhou, Henan Province, China; Corresponding author. The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, 9 Renmin Road, Zhengzhou, Henan Province, 450004, China.School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan Province, China; Corresponding author. School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan Province, 450001, China.Background: Caveolin-1, the scaffolding protein of cholesterol-rich invaginations, plays an important role in store-operated Ca2+ influx and its phosphorylation at Tyr14 (p-caveolin-1) is vital to mobilize protection against myocardial ischemia (MI) injury. SOCE, comprising STIM1, ORAI1 and TRPC1, contributes to intracellular Ca2+ ([Ca2+]i) accumulation in cardiomyocytes. The purified extract of steamed Panax ginseng (EPG) attenuated [Ca2+]i overload against MI injury. Thus, the aim of this study was to investigate the possibility of EPG affecting p-caveolin-1 to further mediate SOCE/[Ca2+]i against MI injury in neonatal rat cardiomyocytes and a rat model. Methods: PP2, an inhibitor of p-caveolin-1, was used. Cell viability, [Ca2+]i concentration were analyzed in cardiomyocytes. In rats, myocardial infarct size, pathological damages, apoptosis and cardiac fibrosis were evaluated, p-caveolin-1 and STIM1 were detected by immunofluorescence, and the levels of caveolin-1, STIM1, ORAI1 and TRPC1 were determined by RT-PCR and Western blot. And, release of LDH, cTnI and BNP was measured. Results: EPG, ginsenosides accounting for 57.96%, suppressed release of LDH, cTnI and BNP, and protected cardiomyocytes by inhibiting Ca2+ influx. And, EPG significantly relieved myocardial infarct size, cardiac apoptosis, fibrosis, and ultrastructure abnormality. Moreover, EPG negatively regulated SOCE via increasing p-caveolin-1 protein, decreasing ORAI1 mRNA and protein levels of ORAI1, TRPC1 and STIM1. More importantly, inhibition of the p-caveolin-1 significantly suppressed all of the above cardioprotection of EPG. Conclusions: Caveolin-1 phosphorylation is involved in the protective effects of EPG against MI injury via increasing p-caveolin-1 to negatively regulate SOCE/[Ca2+]i.http://www.sciencedirect.com/science/article/pii/S1226845323000775Panax ginsengmyocardial ischemiacaveolin-1calcium overloadSOCE
spellingShingle Hai-Xia Li
Yan Ma
Yu-Xiao Yan
Xin-Ke Zhai
Meng-Yu Xin
Tian Wang
Dong-Cao Xu
Yu-Tong Song
Chun-Dong Song
Cheng-Xue Pan
The purified extract of steamed Panax ginseng protects cardiomyocyte from ischemic injury via caveolin-1 phosphorylation-mediating calcium influx
Journal of Ginseng Research
Panax ginseng
myocardial ischemia
caveolin-1
calcium overload
SOCE
title The purified extract of steamed Panax ginseng protects cardiomyocyte from ischemic injury via caveolin-1 phosphorylation-mediating calcium influx
title_full The purified extract of steamed Panax ginseng protects cardiomyocyte from ischemic injury via caveolin-1 phosphorylation-mediating calcium influx
title_fullStr The purified extract of steamed Panax ginseng protects cardiomyocyte from ischemic injury via caveolin-1 phosphorylation-mediating calcium influx
title_full_unstemmed The purified extract of steamed Panax ginseng protects cardiomyocyte from ischemic injury via caveolin-1 phosphorylation-mediating calcium influx
title_short The purified extract of steamed Panax ginseng protects cardiomyocyte from ischemic injury via caveolin-1 phosphorylation-mediating calcium influx
title_sort purified extract of steamed panax ginseng protects cardiomyocyte from ischemic injury via caveolin 1 phosphorylation mediating calcium influx
topic Panax ginseng
myocardial ischemia
caveolin-1
calcium overload
SOCE
url http://www.sciencedirect.com/science/article/pii/S1226845323000775
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