Cargando…

Protective effects of Araloside C against myocardial ischaemia/reperfusion injury: potential involvement of heat shock protein 90

The present study was designed to investigate whether Araloside C, one of the major triterpenoid compounds isolated from Aralia elata known to be cardioprotective, can improve heart function following ischaemia/reperfusion (I/R) injury and elucidate its underlying mechanisms. We observed that Aralos...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Min, Tian, Yu, Du, Yu‐yang, Sun, Gui‐bo, Xu, Xu‐dong, Jiang, Hai, Xu, Hui‐bo, Meng, Xiang‐bao, Zhang, Jing‐yi, Ding, Shi‐lan, Zhang, Miao‐di, Yang, Ming‐hua, Sun, Xiao‐bo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5571541/
https://www.ncbi.nlm.nih.gov/pubmed/28225183
http://dx.doi.org/10.1111/jcmm.13107
_version_ 1783259361485783040
author Wang, Min
Tian, Yu
Du, Yu‐yang
Sun, Gui‐bo
Xu, Xu‐dong
Jiang, Hai
Xu, Hui‐bo
Meng, Xiang‐bao
Zhang, Jing‐yi
Ding, Shi‐lan
Zhang, Miao‐di
Yang, Ming‐hua
Sun, Xiao‐bo
author_facet Wang, Min
Tian, Yu
Du, Yu‐yang
Sun, Gui‐bo
Xu, Xu‐dong
Jiang, Hai
Xu, Hui‐bo
Meng, Xiang‐bao
Zhang, Jing‐yi
Ding, Shi‐lan
Zhang, Miao‐di
Yang, Ming‐hua
Sun, Xiao‐bo
author_sort Wang, Min
collection PubMed
description The present study was designed to investigate whether Araloside C, one of the major triterpenoid compounds isolated from Aralia elata known to be cardioprotective, can improve heart function following ischaemia/reperfusion (I/R) injury and elucidate its underlying mechanisms. We observed that Araloside C concentration‐dependently improved cardiac function and depressed oxidative stress induced by I/R. Similar protection was confirmed in isolated cardiomyocytes characterized by maintaining Ca(2+) transients and cell shortening against I/R. Moreover, the potential targets of Araloside C were predicted using the DDI‐CPI server and Discovery Studio software. Molecular docking analysis revealed that Araloside C could be stably docked into the ATP/ADP‐binding domain of the heat shock protein 90 (Hsp90) protein via the formation of hydrogen bonds. The binding affinity of Hsp90 to Araloside C was detected using nanopore optical interferometry and yielded KD values of 29 μM. Araloside C also up‐regulated the expression levels of Hsp90 and improved cell viability in hypoxia/reoxygenation‐treated H9c2 cardiomyocytes, whereas the addition of 17‐AAG, a pharmacologic inhibitor of Hsp90, attenuated Araloside C‐induced cardioprotective effect. These findings reveal that Araloside C can efficiently attenuate myocardial I/R injury by reducing I/R‐induced oxidative stress and [Ca(2+)](i) overload, which was possibly related to its binding to the Hsp90 protein.
format Online
Article
Text
id pubmed-5571541
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-55715412017-09-01 Protective effects of Araloside C against myocardial ischaemia/reperfusion injury: potential involvement of heat shock protein 90 Wang, Min Tian, Yu Du, Yu‐yang Sun, Gui‐bo Xu, Xu‐dong Jiang, Hai Xu, Hui‐bo Meng, Xiang‐bao Zhang, Jing‐yi Ding, Shi‐lan Zhang, Miao‐di Yang, Ming‐hua Sun, Xiao‐bo J Cell Mol Med Original Articles The present study was designed to investigate whether Araloside C, one of the major triterpenoid compounds isolated from Aralia elata known to be cardioprotective, can improve heart function following ischaemia/reperfusion (I/R) injury and elucidate its underlying mechanisms. We observed that Araloside C concentration‐dependently improved cardiac function and depressed oxidative stress induced by I/R. Similar protection was confirmed in isolated cardiomyocytes characterized by maintaining Ca(2+) transients and cell shortening against I/R. Moreover, the potential targets of Araloside C were predicted using the DDI‐CPI server and Discovery Studio software. Molecular docking analysis revealed that Araloside C could be stably docked into the ATP/ADP‐binding domain of the heat shock protein 90 (Hsp90) protein via the formation of hydrogen bonds. The binding affinity of Hsp90 to Araloside C was detected using nanopore optical interferometry and yielded KD values of 29 μM. Araloside C also up‐regulated the expression levels of Hsp90 and improved cell viability in hypoxia/reoxygenation‐treated H9c2 cardiomyocytes, whereas the addition of 17‐AAG, a pharmacologic inhibitor of Hsp90, attenuated Araloside C‐induced cardioprotective effect. These findings reveal that Araloside C can efficiently attenuate myocardial I/R injury by reducing I/R‐induced oxidative stress and [Ca(2+)](i) overload, which was possibly related to its binding to the Hsp90 protein. John Wiley and Sons Inc. 2017-02-22 2017-09 /pmc/articles/PMC5571541/ /pubmed/28225183 http://dx.doi.org/10.1111/jcmm.13107 Text en © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Wang, Min
Tian, Yu
Du, Yu‐yang
Sun, Gui‐bo
Xu, Xu‐dong
Jiang, Hai
Xu, Hui‐bo
Meng, Xiang‐bao
Zhang, Jing‐yi
Ding, Shi‐lan
Zhang, Miao‐di
Yang, Ming‐hua
Sun, Xiao‐bo
Protective effects of Araloside C against myocardial ischaemia/reperfusion injury: potential involvement of heat shock protein 90
title Protective effects of Araloside C against myocardial ischaemia/reperfusion injury: potential involvement of heat shock protein 90
title_full Protective effects of Araloside C against myocardial ischaemia/reperfusion injury: potential involvement of heat shock protein 90
title_fullStr Protective effects of Araloside C against myocardial ischaemia/reperfusion injury: potential involvement of heat shock protein 90
title_full_unstemmed Protective effects of Araloside C against myocardial ischaemia/reperfusion injury: potential involvement of heat shock protein 90
title_short Protective effects of Araloside C against myocardial ischaemia/reperfusion injury: potential involvement of heat shock protein 90
title_sort protective effects of araloside c against myocardial ischaemia/reperfusion injury: potential involvement of heat shock protein 90
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5571541/
https://www.ncbi.nlm.nih.gov/pubmed/28225183
http://dx.doi.org/10.1111/jcmm.13107
work_keys_str_mv AT wangmin protectiveeffectsofaralosidecagainstmyocardialischaemiareperfusioninjurypotentialinvolvementofheatshockprotein90
AT tianyu protectiveeffectsofaralosidecagainstmyocardialischaemiareperfusioninjurypotentialinvolvementofheatshockprotein90
AT duyuyang protectiveeffectsofaralosidecagainstmyocardialischaemiareperfusioninjurypotentialinvolvementofheatshockprotein90
AT sunguibo protectiveeffectsofaralosidecagainstmyocardialischaemiareperfusioninjurypotentialinvolvementofheatshockprotein90
AT xuxudong protectiveeffectsofaralosidecagainstmyocardialischaemiareperfusioninjurypotentialinvolvementofheatshockprotein90
AT jianghai protectiveeffectsofaralosidecagainstmyocardialischaemiareperfusioninjurypotentialinvolvementofheatshockprotein90
AT xuhuibo protectiveeffectsofaralosidecagainstmyocardialischaemiareperfusioninjurypotentialinvolvementofheatshockprotein90
AT mengxiangbao protectiveeffectsofaralosidecagainstmyocardialischaemiareperfusioninjurypotentialinvolvementofheatshockprotein90
AT zhangjingyi protectiveeffectsofaralosidecagainstmyocardialischaemiareperfusioninjurypotentialinvolvementofheatshockprotein90
AT dingshilan protectiveeffectsofaralosidecagainstmyocardialischaemiareperfusioninjurypotentialinvolvementofheatshockprotein90
AT zhangmiaodi protectiveeffectsofaralosidecagainstmyocardialischaemiareperfusioninjurypotentialinvolvementofheatshockprotein90
AT yangminghua protectiveeffectsofaralosidecagainstmyocardialischaemiareperfusioninjurypotentialinvolvementofheatshockprotein90
AT sunxiaobo protectiveeffectsofaralosidecagainstmyocardialischaemiareperfusioninjurypotentialinvolvementofheatshockprotein90