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Endoplasmic Reticulum Stress Cooperates in Silica Nanoparticles-Induced Macrophage Apoptosis via Activation of CHOP-Mediated Apoptotic Signaling Pathway
While silica nanoparticles (SiNPs) have wide applications, they inevitably increase atmospheric particulate matter and human exposure to this nanomaterial. Numerous studies have focused on how to disclose SiNP toxicity and on understanding its toxic mechanisms. However, there are few studies in the...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929173/ https://www.ncbi.nlm.nih.gov/pubmed/31766455 http://dx.doi.org/10.3390/ijms20235846 |
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author | Chen, Fenglei Jin, Jiaqi Hu, Jiahui Wang, Yujing Ma, Zhiyu Zhang, Jinlong |
author_facet | Chen, Fenglei Jin, Jiaqi Hu, Jiahui Wang, Yujing Ma, Zhiyu Zhang, Jinlong |
author_sort | Chen, Fenglei |
collection | PubMed |
description | While silica nanoparticles (SiNPs) have wide applications, they inevitably increase atmospheric particulate matter and human exposure to this nanomaterial. Numerous studies have focused on how to disclose SiNP toxicity and on understanding its toxic mechanisms. However, there are few studies in the literature reporting the interaction between endoplasmic reticulum (ER) stress and SiNP exposure, and the corresponding detailed mechanisms have not been clearly determined. In this study, CCK-8 and flow cytometry assays demonstrated that SiNPs gradually decreased cell viability and increased cell apoptosis in RAW 264.7 macrophage cells in dose- and time-dependent manners. Western blot analysis showed that SiNPs significantly activated ER stress by upregulating GRP78, CHOP, and ERO1α expression. Meanwhile, western blot analysis also showed that SiNPs activated the mitochondrial-mediated apoptotic signaling pathway by upregulating BAD and Caspase-3, and downregulating the BCL-2/BAX ratio. Moreover, 4-phenylbutyrate (4-PBA), an ER stress inhibitor, significantly decreased GRP78, CHOP, and ERO1α expression, and inhibited cell apoptosis in RAW 264.7 macrophage cells. Furthermore, overexpression of CHOP significantly enhanced cell apoptosis, while knockdown of CHOP significantly protected RAW 264.7 macrophage cells from apoptosis induced by SiNPs. We found that the CHOP-ERO1α-caspase-dependent apoptotic signaling pathway was activated by upregulating the downstream target protein ERO1α and caspase-dependent mitochondrial-mediated apoptotic signaling pathway by upregulating Caspase-3 and downregulating the ratio of BCL-2/BAX. In summary, ER stress participated in cell apoptosis induced by SiNPs and CHOP regulated SiNP-induced cell apoptosis, at least partly, via activation of the CHOP-ERO1α-caspase apoptotic signaling pathway in RAW 264.7 macrophage cells. |
format | Online Article Text |
id | pubmed-6929173 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-69291732019-12-26 Endoplasmic Reticulum Stress Cooperates in Silica Nanoparticles-Induced Macrophage Apoptosis via Activation of CHOP-Mediated Apoptotic Signaling Pathway Chen, Fenglei Jin, Jiaqi Hu, Jiahui Wang, Yujing Ma, Zhiyu Zhang, Jinlong Int J Mol Sci Article While silica nanoparticles (SiNPs) have wide applications, they inevitably increase atmospheric particulate matter and human exposure to this nanomaterial. Numerous studies have focused on how to disclose SiNP toxicity and on understanding its toxic mechanisms. However, there are few studies in the literature reporting the interaction between endoplasmic reticulum (ER) stress and SiNP exposure, and the corresponding detailed mechanisms have not been clearly determined. In this study, CCK-8 and flow cytometry assays demonstrated that SiNPs gradually decreased cell viability and increased cell apoptosis in RAW 264.7 macrophage cells in dose- and time-dependent manners. Western blot analysis showed that SiNPs significantly activated ER stress by upregulating GRP78, CHOP, and ERO1α expression. Meanwhile, western blot analysis also showed that SiNPs activated the mitochondrial-mediated apoptotic signaling pathway by upregulating BAD and Caspase-3, and downregulating the BCL-2/BAX ratio. Moreover, 4-phenylbutyrate (4-PBA), an ER stress inhibitor, significantly decreased GRP78, CHOP, and ERO1α expression, and inhibited cell apoptosis in RAW 264.7 macrophage cells. Furthermore, overexpression of CHOP significantly enhanced cell apoptosis, while knockdown of CHOP significantly protected RAW 264.7 macrophage cells from apoptosis induced by SiNPs. We found that the CHOP-ERO1α-caspase-dependent apoptotic signaling pathway was activated by upregulating the downstream target protein ERO1α and caspase-dependent mitochondrial-mediated apoptotic signaling pathway by upregulating Caspase-3 and downregulating the ratio of BCL-2/BAX. In summary, ER stress participated in cell apoptosis induced by SiNPs and CHOP regulated SiNP-induced cell apoptosis, at least partly, via activation of the CHOP-ERO1α-caspase apoptotic signaling pathway in RAW 264.7 macrophage cells. MDPI 2019-11-21 /pmc/articles/PMC6929173/ /pubmed/31766455 http://dx.doi.org/10.3390/ijms20235846 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 Chen, Fenglei Jin, Jiaqi Hu, Jiahui Wang, Yujing Ma, Zhiyu Zhang, Jinlong Endoplasmic Reticulum Stress Cooperates in Silica Nanoparticles-Induced Macrophage Apoptosis via Activation of CHOP-Mediated Apoptotic Signaling Pathway |
title | Endoplasmic Reticulum Stress Cooperates in Silica Nanoparticles-Induced Macrophage Apoptosis via Activation of CHOP-Mediated Apoptotic Signaling Pathway |
title_full | Endoplasmic Reticulum Stress Cooperates in Silica Nanoparticles-Induced Macrophage Apoptosis via Activation of CHOP-Mediated Apoptotic Signaling Pathway |
title_fullStr | Endoplasmic Reticulum Stress Cooperates in Silica Nanoparticles-Induced Macrophage Apoptosis via Activation of CHOP-Mediated Apoptotic Signaling Pathway |
title_full_unstemmed | Endoplasmic Reticulum Stress Cooperates in Silica Nanoparticles-Induced Macrophage Apoptosis via Activation of CHOP-Mediated Apoptotic Signaling Pathway |
title_short | Endoplasmic Reticulum Stress Cooperates in Silica Nanoparticles-Induced Macrophage Apoptosis via Activation of CHOP-Mediated Apoptotic Signaling Pathway |
title_sort | endoplasmic reticulum stress cooperates in silica nanoparticles-induced macrophage apoptosis via activation of chop-mediated apoptotic signaling pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929173/ https://www.ncbi.nlm.nih.gov/pubmed/31766455 http://dx.doi.org/10.3390/ijms20235846 |
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