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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Language: | English |
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Elsevier
2023-11-01
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Series: | Journal of Ginseng Research |
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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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language | English |
last_indexed | 2024-03-11T03:13:35Z |
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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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