Araloside C Prevents Hypoxia/Reoxygenation-Induced Endoplasmic Reticulum Stress via Increasing Heat Shock Protein 90 in H9c2 Cardiomyocytes

Araloside C (AsC) is a cardioprotective triterpenoid compound that is mainly isolated from Aralia elata. This study aims to determine the effects of AsC on hypoxia-reoxygenation (H/R)-induced apoptosis in H9c2 cardiomyocytes and its underlying mechanisms. Results demonstrated that pretreatment with...

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Main Authors: Yuyang Du, Min Wang, Xuesong Liu, Jingyi Zhang, Xudong Xu, Huibo Xu, Guibo Sun, Xiaobo Sun
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-04-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:http://journal.frontiersin.org/article/10.3389/fphar.2018.00180/full
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author Yuyang Du
Yuyang Du
Min Wang
Min Wang
Xuesong Liu
Jingyi Zhang
Jingyi Zhang
Xudong Xu
Xudong Xu
Huibo Xu
Guibo Sun
Guibo Sun
Xiaobo Sun
Xiaobo Sun
author_facet Yuyang Du
Yuyang Du
Min Wang
Min Wang
Xuesong Liu
Jingyi Zhang
Jingyi Zhang
Xudong Xu
Xudong Xu
Huibo Xu
Guibo Sun
Guibo Sun
Xiaobo Sun
Xiaobo Sun
author_sort Yuyang Du
collection DOAJ
description Araloside C (AsC) is a cardioprotective triterpenoid compound that is mainly isolated from Aralia elata. This study aims to determine the effects of AsC on hypoxia-reoxygenation (H/R)-induced apoptosis in H9c2 cardiomyocytes and its underlying mechanisms. Results demonstrated that pretreatment with AsC (12.5 μM) for 12 h significantly suppressed the H/R injury in H9c2 cardiomyocytes, including improving cell viability, attenuating the LDH leakage and preventing cardiomyocyte apoptosis. AsC also inhibited H/R-induced ER stress by reducing the activation of ER stress pathways (PERK/eIF2α and ATF6), and decreasing the expression of ER stress-related apoptotic proteins (CHOP and caspase-12). Moreover, AsC greatly improved the expression level of HSP90 compared with that in the H/R group. The use of HSP90 inhibitor 17-AAG and HSP90 siRNA blocked the above suppression effect of AsC on ER stress-related apoptosis caused by H/R. Taken together, AsC could reduce H/R-induced apoptosis possibly because it attenuates ER stress-dependent apoptotic pathways by increasing HSP90 expression.
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spelling doaj.art-1d2ba5d4046841538454757ab76714792022-12-22T03:17:51ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-04-01910.3389/fphar.2018.00180323755Araloside C Prevents Hypoxia/Reoxygenation-Induced Endoplasmic Reticulum Stress via Increasing Heat Shock Protein 90 in H9c2 CardiomyocytesYuyang Du0Yuyang Du1Min Wang2Min Wang3Xuesong Liu4Jingyi Zhang5Jingyi Zhang6Xudong Xu7Xudong Xu8Huibo Xu9Guibo Sun10Guibo Sun11Xiaobo Sun12Xiaobo Sun13Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBeijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing, ChinaInstitute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBeijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing, ChinaCenter of Research and Development on Life Sciences and Environmental Sciences, Harbin University of Commerce, Harbin, ChinaInstitute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBeijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing, ChinaInstitute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBeijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing, ChinaAcademy of Chinese Medical Sciences of Jilin Province, Changchun, ChinaInstitute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBeijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing, ChinaInstitute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBeijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing, ChinaAraloside C (AsC) is a cardioprotective triterpenoid compound that is mainly isolated from Aralia elata. This study aims to determine the effects of AsC on hypoxia-reoxygenation (H/R)-induced apoptosis in H9c2 cardiomyocytes and its underlying mechanisms. Results demonstrated that pretreatment with AsC (12.5 μM) for 12 h significantly suppressed the H/R injury in H9c2 cardiomyocytes, including improving cell viability, attenuating the LDH leakage and preventing cardiomyocyte apoptosis. AsC also inhibited H/R-induced ER stress by reducing the activation of ER stress pathways (PERK/eIF2α and ATF6), and decreasing the expression of ER stress-related apoptotic proteins (CHOP and caspase-12). Moreover, AsC greatly improved the expression level of HSP90 compared with that in the H/R group. The use of HSP90 inhibitor 17-AAG and HSP90 siRNA blocked the above suppression effect of AsC on ER stress-related apoptosis caused by H/R. Taken together, AsC could reduce H/R-induced apoptosis possibly because it attenuates ER stress-dependent apoptotic pathways by increasing HSP90 expression.http://journal.frontiersin.org/article/10.3389/fphar.2018.00180/fullAraloside Chypoxia/reoxygenation injuryendoplasmic reticulum stressheat shock protein 90apoptosis
spellingShingle Yuyang Du
Yuyang Du
Min Wang
Min Wang
Xuesong Liu
Jingyi Zhang
Jingyi Zhang
Xudong Xu
Xudong Xu
Huibo Xu
Guibo Sun
Guibo Sun
Xiaobo Sun
Xiaobo Sun
Araloside C Prevents Hypoxia/Reoxygenation-Induced Endoplasmic Reticulum Stress via Increasing Heat Shock Protein 90 in H9c2 Cardiomyocytes
Frontiers in Pharmacology
Araloside C
hypoxia/reoxygenation injury
endoplasmic reticulum stress
heat shock protein 90
apoptosis
title Araloside C Prevents Hypoxia/Reoxygenation-Induced Endoplasmic Reticulum Stress via Increasing Heat Shock Protein 90 in H9c2 Cardiomyocytes
title_full Araloside C Prevents Hypoxia/Reoxygenation-Induced Endoplasmic Reticulum Stress via Increasing Heat Shock Protein 90 in H9c2 Cardiomyocytes
title_fullStr Araloside C Prevents Hypoxia/Reoxygenation-Induced Endoplasmic Reticulum Stress via Increasing Heat Shock Protein 90 in H9c2 Cardiomyocytes
title_full_unstemmed Araloside C Prevents Hypoxia/Reoxygenation-Induced Endoplasmic Reticulum Stress via Increasing Heat Shock Protein 90 in H9c2 Cardiomyocytes
title_short Araloside C Prevents Hypoxia/Reoxygenation-Induced Endoplasmic Reticulum Stress via Increasing Heat Shock Protein 90 in H9c2 Cardiomyocytes
title_sort araloside c prevents hypoxia reoxygenation induced endoplasmic reticulum stress via increasing heat shock protein 90 in h9c2 cardiomyocytes
topic Araloside C
hypoxia/reoxygenation injury
endoplasmic reticulum stress
heat shock protein 90
apoptosis
url http://journal.frontiersin.org/article/10.3389/fphar.2018.00180/full
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