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Sodium danshensu attenuates cerebral ischemia–reperfusion injury by targeting AKT1
The beneficial properties of Sodium Danshensu (SDSS) for controlling cerebral ischemia and reperfusion injury (CIRI) are elucidated here both in vivo and in vitro. SDSS administration significantly improved the viability of P12 cells, reduced lactate dehydrogenase (LDH) leakage, and decreased the ap...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9520076/ https://www.ncbi.nlm.nih.gov/pubmed/36188542 http://dx.doi.org/10.3389/fphar.2022.946668 |
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author | Gao, Qing Deng, Hao Yang, Zhengfei Yang, Qiuyue Zhang, Yilin Yuan, Xiaopeng Zeng, Miao Guo, Maojuan Zeng, Wenyun Jiang, Xijuan Yu, Bin |
author_facet | Gao, Qing Deng, Hao Yang, Zhengfei Yang, Qiuyue Zhang, Yilin Yuan, Xiaopeng Zeng, Miao Guo, Maojuan Zeng, Wenyun Jiang, Xijuan Yu, Bin |
author_sort | Gao, Qing |
collection | PubMed |
description | The beneficial properties of Sodium Danshensu (SDSS) for controlling cerebral ischemia and reperfusion injury (CIRI) are elucidated here both in vivo and in vitro. SDSS administration significantly improved the viability of P12 cells, reduced lactate dehydrogenase (LDH) leakage, and decreased the apoptosis rate following exposure to an oxygen-glucose deprivation/reoxygenation (OGD) environment. In addition, the results of a Huprot(TM) human protein microarray and network pharmacology indicated that AKT1 is one of the main targets of SDSS. Moreover, functional experiments showed that SDSS intervention markedly increased the phosphorylation level of AKT1 and its downstream regulator, mTOR. The binding sites of SDSS to AKT1 protein were confirmed by Autodock software and a surface plasmon resonance experiment, the result of which imply that SDSS targets to the PH domain of AKT1 at ASN-53, ARG-86, and LYS-14 residues. Furthermore, knockdown of AKT1 significantly abolished the role of SDSS in protecting cells from apoptosis and necrosis. Finally, we investigated the curative effect of SDSS in a rat model of CIRI. The results suggest that administration of SDSS significantly reduces CIRI-induced necrosis and apoptosis in brain samples by activating AKT1 protein. In conclusion, SDSS exerts its positive role in alleviating CIRI by binding to the PH domain of AKT1 protein, further resulting in AKT1 activation. |
format | Online Article Text |
id | pubmed-9520076 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95200762022-09-30 Sodium danshensu attenuates cerebral ischemia–reperfusion injury by targeting AKT1 Gao, Qing Deng, Hao Yang, Zhengfei Yang, Qiuyue Zhang, Yilin Yuan, Xiaopeng Zeng, Miao Guo, Maojuan Zeng, Wenyun Jiang, Xijuan Yu, Bin Front Pharmacol Pharmacology The beneficial properties of Sodium Danshensu (SDSS) for controlling cerebral ischemia and reperfusion injury (CIRI) are elucidated here both in vivo and in vitro. SDSS administration significantly improved the viability of P12 cells, reduced lactate dehydrogenase (LDH) leakage, and decreased the apoptosis rate following exposure to an oxygen-glucose deprivation/reoxygenation (OGD) environment. In addition, the results of a Huprot(TM) human protein microarray and network pharmacology indicated that AKT1 is one of the main targets of SDSS. Moreover, functional experiments showed that SDSS intervention markedly increased the phosphorylation level of AKT1 and its downstream regulator, mTOR. The binding sites of SDSS to AKT1 protein were confirmed by Autodock software and a surface plasmon resonance experiment, the result of which imply that SDSS targets to the PH domain of AKT1 at ASN-53, ARG-86, and LYS-14 residues. Furthermore, knockdown of AKT1 significantly abolished the role of SDSS in protecting cells from apoptosis and necrosis. Finally, we investigated the curative effect of SDSS in a rat model of CIRI. The results suggest that administration of SDSS significantly reduces CIRI-induced necrosis and apoptosis in brain samples by activating AKT1 protein. In conclusion, SDSS exerts its positive role in alleviating CIRI by binding to the PH domain of AKT1 protein, further resulting in AKT1 activation. Frontiers Media S.A. 2022-09-15 /pmc/articles/PMC9520076/ /pubmed/36188542 http://dx.doi.org/10.3389/fphar.2022.946668 Text en Copyright © 2022 Gao, Deng, Yang, Yang, Zhang, Yuan, Zeng, Guo, Zeng, Jiang and Yu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Gao, Qing Deng, Hao Yang, Zhengfei Yang, Qiuyue Zhang, Yilin Yuan, Xiaopeng Zeng, Miao Guo, Maojuan Zeng, Wenyun Jiang, Xijuan Yu, Bin Sodium danshensu attenuates cerebral ischemia–reperfusion injury by targeting AKT1 |
title | Sodium danshensu attenuates cerebral ischemia–reperfusion injury by targeting AKT1 |
title_full | Sodium danshensu attenuates cerebral ischemia–reperfusion injury by targeting AKT1 |
title_fullStr | Sodium danshensu attenuates cerebral ischemia–reperfusion injury by targeting AKT1 |
title_full_unstemmed | Sodium danshensu attenuates cerebral ischemia–reperfusion injury by targeting AKT1 |
title_short | Sodium danshensu attenuates cerebral ischemia–reperfusion injury by targeting AKT1 |
title_sort | sodium danshensu attenuates cerebral ischemia–reperfusion injury by targeting akt1 |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9520076/ https://www.ncbi.nlm.nih.gov/pubmed/36188542 http://dx.doi.org/10.3389/fphar.2022.946668 |
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