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KMID : 0352720230470060755
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Journal of Ginseng Research
2023 Volume.47 No. 6 p.755 ~ p.765
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The purified extract of steamed Panax ginseng protects cardiomyocyte from ischemic injury via caveolin-1 phosphorylation-mediating calcium influx
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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
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Abstract
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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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KEYWORD
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Panax ginseng, myocardial ischemia, caveolin-1, calcium overload, SOCE
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