Cargando…

Ginsenoside Re Inhibits ROS/ASK-1 Dependent Mitochondrial Apoptosis Pathway and Activation of Nrf2-Antioxidant Response in Beta-Amyloid-Challenged SH-SY5Y Cells

Accumulation of amyloid-β (Aβ), which results in the formation of senile plaques that cause oxidative damage and neuronal cell death, has been accepted as the major pathological mechanism of Alzheimer’s disease (AD). Hence, inhibition of Aβ-induced oxidative damage and neuronal cell apoptosis repres...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Meichen, Bai, Xueyuan, Yu, Shiting, Zhao, Wenxue, Qiao, Juhui, Liu, Ying, Zhao, Daqing, Wang, Jiawen, Wang, Siming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6696356/
https://www.ncbi.nlm.nih.gov/pubmed/31344860
http://dx.doi.org/10.3390/molecules24152687
_version_ 1783444251395227648
author Liu, Meichen
Bai, Xueyuan
Yu, Shiting
Zhao, Wenxue
Qiao, Juhui
Liu, Ying
Zhao, Daqing
Wang, Jiawen
Wang, Siming
author_facet Liu, Meichen
Bai, Xueyuan
Yu, Shiting
Zhao, Wenxue
Qiao, Juhui
Liu, Ying
Zhao, Daqing
Wang, Jiawen
Wang, Siming
author_sort Liu, Meichen
collection PubMed
description Accumulation of amyloid-β (Aβ), which results in the formation of senile plaques that cause oxidative damage and neuronal cell death, has been accepted as the major pathological mechanism of Alzheimer’s disease (AD). Hence, inhibition of Aβ-induced oxidative damage and neuronal cell apoptosis represents the effective strategies in combating AD. Ginsenoside Re (Re) has pharmacological effects against Aβ-induced neurotoxicity. However, its molecular mechanism remains elusive. The present study evaluated the effect of Re against Aβ-induced cytotoxicity and apoptosis in SH-SY5Y cells, and investigated the underlying mechanism. We demonstrate that Re inhibits the Aβ-triggered mitochondrial apoptotic pathway, as indicated by maintenance of mitochondrial functional, elevated Bcl-2/Bax ratio, reduced cytochrome c release, and inactivation of caspase-3/9. Re attenuated Aβ-evoked reactive oxygen species (ROS) production, apoptosis signal-regulating kinase 1 (ASK1) phosphorylation, and JNK activation. ROS-scavenging abrogated the ability of Re to alter ASK-1 activation. Simultaneously, inhibition of JNK abolished Re-induced Bax downregulation in Aβ-challenged SH-SY5Y cells. In addition, Re enhanced activation of the nuclear factor-E2-related factor 2 (Nrf2) in Aβ-induced SH-SY5Y cells. Knockdown of Nrf2 by small interfering RNA targeting Nrf2 abolished the protective effect of Re. Our findings indicate that Re could be a potential therapeutic approach for the treatment of AD.
format Online
Article
Text
id pubmed-6696356
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-66963562019-09-05 Ginsenoside Re Inhibits ROS/ASK-1 Dependent Mitochondrial Apoptosis Pathway and Activation of Nrf2-Antioxidant Response in Beta-Amyloid-Challenged SH-SY5Y Cells Liu, Meichen Bai, Xueyuan Yu, Shiting Zhao, Wenxue Qiao, Juhui Liu, Ying Zhao, Daqing Wang, Jiawen Wang, Siming Molecules Article Accumulation of amyloid-β (Aβ), which results in the formation of senile plaques that cause oxidative damage and neuronal cell death, has been accepted as the major pathological mechanism of Alzheimer’s disease (AD). Hence, inhibition of Aβ-induced oxidative damage and neuronal cell apoptosis represents the effective strategies in combating AD. Ginsenoside Re (Re) has pharmacological effects against Aβ-induced neurotoxicity. However, its molecular mechanism remains elusive. The present study evaluated the effect of Re against Aβ-induced cytotoxicity and apoptosis in SH-SY5Y cells, and investigated the underlying mechanism. We demonstrate that Re inhibits the Aβ-triggered mitochondrial apoptotic pathway, as indicated by maintenance of mitochondrial functional, elevated Bcl-2/Bax ratio, reduced cytochrome c release, and inactivation of caspase-3/9. Re attenuated Aβ-evoked reactive oxygen species (ROS) production, apoptosis signal-regulating kinase 1 (ASK1) phosphorylation, and JNK activation. ROS-scavenging abrogated the ability of Re to alter ASK-1 activation. Simultaneously, inhibition of JNK abolished Re-induced Bax downregulation in Aβ-challenged SH-SY5Y cells. In addition, Re enhanced activation of the nuclear factor-E2-related factor 2 (Nrf2) in Aβ-induced SH-SY5Y cells. Knockdown of Nrf2 by small interfering RNA targeting Nrf2 abolished the protective effect of Re. Our findings indicate that Re could be a potential therapeutic approach for the treatment of AD. MDPI 2019-07-24 /pmc/articles/PMC6696356/ /pubmed/31344860 http://dx.doi.org/10.3390/molecules24152687 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liu, Meichen
Bai, Xueyuan
Yu, Shiting
Zhao, Wenxue
Qiao, Juhui
Liu, Ying
Zhao, Daqing
Wang, Jiawen
Wang, Siming
Ginsenoside Re Inhibits ROS/ASK-1 Dependent Mitochondrial Apoptosis Pathway and Activation of Nrf2-Antioxidant Response in Beta-Amyloid-Challenged SH-SY5Y Cells
title Ginsenoside Re Inhibits ROS/ASK-1 Dependent Mitochondrial Apoptosis Pathway and Activation of Nrf2-Antioxidant Response in Beta-Amyloid-Challenged SH-SY5Y Cells
title_full Ginsenoside Re Inhibits ROS/ASK-1 Dependent Mitochondrial Apoptosis Pathway and Activation of Nrf2-Antioxidant Response in Beta-Amyloid-Challenged SH-SY5Y Cells
title_fullStr Ginsenoside Re Inhibits ROS/ASK-1 Dependent Mitochondrial Apoptosis Pathway and Activation of Nrf2-Antioxidant Response in Beta-Amyloid-Challenged SH-SY5Y Cells
title_full_unstemmed Ginsenoside Re Inhibits ROS/ASK-1 Dependent Mitochondrial Apoptosis Pathway and Activation of Nrf2-Antioxidant Response in Beta-Amyloid-Challenged SH-SY5Y Cells
title_short Ginsenoside Re Inhibits ROS/ASK-1 Dependent Mitochondrial Apoptosis Pathway and Activation of Nrf2-Antioxidant Response in Beta-Amyloid-Challenged SH-SY5Y Cells
title_sort ginsenoside re inhibits ros/ask-1 dependent mitochondrial apoptosis pathway and activation of nrf2-antioxidant response in beta-amyloid-challenged sh-sy5y cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6696356/
https://www.ncbi.nlm.nih.gov/pubmed/31344860
http://dx.doi.org/10.3390/molecules24152687
work_keys_str_mv AT liumeichen ginsenosidereinhibitsrosask1dependentmitochondrialapoptosispathwayandactivationofnrf2antioxidantresponseinbetaamyloidchallengedshsy5ycells
AT baixueyuan ginsenosidereinhibitsrosask1dependentmitochondrialapoptosispathwayandactivationofnrf2antioxidantresponseinbetaamyloidchallengedshsy5ycells
AT yushiting ginsenosidereinhibitsrosask1dependentmitochondrialapoptosispathwayandactivationofnrf2antioxidantresponseinbetaamyloidchallengedshsy5ycells
AT zhaowenxue ginsenosidereinhibitsrosask1dependentmitochondrialapoptosispathwayandactivationofnrf2antioxidantresponseinbetaamyloidchallengedshsy5ycells
AT qiaojuhui ginsenosidereinhibitsrosask1dependentmitochondrialapoptosispathwayandactivationofnrf2antioxidantresponseinbetaamyloidchallengedshsy5ycells
AT liuying ginsenosidereinhibitsrosask1dependentmitochondrialapoptosispathwayandactivationofnrf2antioxidantresponseinbetaamyloidchallengedshsy5ycells
AT zhaodaqing ginsenosidereinhibitsrosask1dependentmitochondrialapoptosispathwayandactivationofnrf2antioxidantresponseinbetaamyloidchallengedshsy5ycells
AT wangjiawen ginsenosidereinhibitsrosask1dependentmitochondrialapoptosispathwayandactivationofnrf2antioxidantresponseinbetaamyloidchallengedshsy5ycells
AT wangsiming ginsenosidereinhibitsrosask1dependentmitochondrialapoptosispathwayandactivationofnrf2antioxidantresponseinbetaamyloidchallengedshsy5ycells