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Sulforaphane Delays Intervertebral Disc Degeneration by Alleviating Endoplasmic Reticulum Stress in Nucleus Pulposus Cells via Activating Nrf-2/HO-1

Intervertebral disc degeneration (IVDD) is one of the main causes of low back pain, which brings heavy burdens to individuals and society. The mechanism of IVDD is complex and diverse. One of the important reasons is that the abnormal accumulation of reactive oxygen species (ROS) in nucleus pulposus...

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Autores principales: Lu, Xiao, Xu, Guangyu, Lin, Zhidi, Song, Jian, Zhang, Yuxuan, Wang, Hongli, Lu, Feizhou, Xia, Xinlei, Ma, Xiaosheng, Zou, Fei, Jiang, Jianyuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9840554/
https://www.ncbi.nlm.nih.gov/pubmed/36647429
http://dx.doi.org/10.1155/2023/3626091
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author Lu, Xiao
Xu, Guangyu
Lin, Zhidi
Song, Jian
Zhang, Yuxuan
Wang, Hongli
Lu, Feizhou
Xia, Xinlei
Ma, Xiaosheng
Zou, Fei
Jiang, Jianyuan
author_facet Lu, Xiao
Xu, Guangyu
Lin, Zhidi
Song, Jian
Zhang, Yuxuan
Wang, Hongli
Lu, Feizhou
Xia, Xinlei
Ma, Xiaosheng
Zou, Fei
Jiang, Jianyuan
author_sort Lu, Xiao
collection PubMed
description Intervertebral disc degeneration (IVDD) is one of the main causes of low back pain, which brings heavy burdens to individuals and society. The mechanism of IVDD is complex and diverse. One of the important reasons is that the abnormal accumulation of reactive oxygen species (ROS) in nucleus pulposus cells (NPCs) leads to endoplasmic reticulum stress (ERS), which causes increased apoptosis of NPCs. Nuclear factor E2-related factor 2 (Nrf-2) and its downstream antioxidant proteins are key molecular switches for sensing oxidative stress and regulating antioxidant responses in cells. Sulforaphane (SFN), a natural compound derived from Brassicaceae plants, is a Nrf-2 agonist that displays potent antioxidant potential in vitro and in vivo. Here, we used advanced glycation end products (AGEs) to construct an in vitro degeneration model of NPCs, and we found that AGEs elevated ROS level in NPCs and caused severe ERS and apoptosis. While SFN can promote the entry of Nrf-2 into the nucleus and increase the expression level of heme oxygenase 1 (HO-1) in vitro, thus clearing the accumulated ROS in cells and alleviating ERS and cell apoptosis. Moreover, the protection of SFN on NPCs was greatly attenuated after HO-1 was inhibited. We also used AGEs to construct a rat IVDD model. Consistent with the in vitro experiments, SFN could attenuate ERS in NPCs in vivo and delay disc degeneration in rats. This study found that SFN can be used as a new and promising agent for the treatment of IVDD.
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spelling pubmed-98405542023-01-15 Sulforaphane Delays Intervertebral Disc Degeneration by Alleviating Endoplasmic Reticulum Stress in Nucleus Pulposus Cells via Activating Nrf-2/HO-1 Lu, Xiao Xu, Guangyu Lin, Zhidi Song, Jian Zhang, Yuxuan Wang, Hongli Lu, Feizhou Xia, Xinlei Ma, Xiaosheng Zou, Fei Jiang, Jianyuan Oxid Med Cell Longev Research Article Intervertebral disc degeneration (IVDD) is one of the main causes of low back pain, which brings heavy burdens to individuals and society. The mechanism of IVDD is complex and diverse. One of the important reasons is that the abnormal accumulation of reactive oxygen species (ROS) in nucleus pulposus cells (NPCs) leads to endoplasmic reticulum stress (ERS), which causes increased apoptosis of NPCs. Nuclear factor E2-related factor 2 (Nrf-2) and its downstream antioxidant proteins are key molecular switches for sensing oxidative stress and regulating antioxidant responses in cells. Sulforaphane (SFN), a natural compound derived from Brassicaceae plants, is a Nrf-2 agonist that displays potent antioxidant potential in vitro and in vivo. Here, we used advanced glycation end products (AGEs) to construct an in vitro degeneration model of NPCs, and we found that AGEs elevated ROS level in NPCs and caused severe ERS and apoptosis. While SFN can promote the entry of Nrf-2 into the nucleus and increase the expression level of heme oxygenase 1 (HO-1) in vitro, thus clearing the accumulated ROS in cells and alleviating ERS and cell apoptosis. Moreover, the protection of SFN on NPCs was greatly attenuated after HO-1 was inhibited. We also used AGEs to construct a rat IVDD model. Consistent with the in vitro experiments, SFN could attenuate ERS in NPCs in vivo and delay disc degeneration in rats. This study found that SFN can be used as a new and promising agent for the treatment of IVDD. Hindawi 2023-01-07 /pmc/articles/PMC9840554/ /pubmed/36647429 http://dx.doi.org/10.1155/2023/3626091 Text en Copyright © 2023 Xiao Lu et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Lu, Xiao
Xu, Guangyu
Lin, Zhidi
Song, Jian
Zhang, Yuxuan
Wang, Hongli
Lu, Feizhou
Xia, Xinlei
Ma, Xiaosheng
Zou, Fei
Jiang, Jianyuan
Sulforaphane Delays Intervertebral Disc Degeneration by Alleviating Endoplasmic Reticulum Stress in Nucleus Pulposus Cells via Activating Nrf-2/HO-1
title Sulforaphane Delays Intervertebral Disc Degeneration by Alleviating Endoplasmic Reticulum Stress in Nucleus Pulposus Cells via Activating Nrf-2/HO-1
title_full Sulforaphane Delays Intervertebral Disc Degeneration by Alleviating Endoplasmic Reticulum Stress in Nucleus Pulposus Cells via Activating Nrf-2/HO-1
title_fullStr Sulforaphane Delays Intervertebral Disc Degeneration by Alleviating Endoplasmic Reticulum Stress in Nucleus Pulposus Cells via Activating Nrf-2/HO-1
title_full_unstemmed Sulforaphane Delays Intervertebral Disc Degeneration by Alleviating Endoplasmic Reticulum Stress in Nucleus Pulposus Cells via Activating Nrf-2/HO-1
title_short Sulforaphane Delays Intervertebral Disc Degeneration by Alleviating Endoplasmic Reticulum Stress in Nucleus Pulposus Cells via Activating Nrf-2/HO-1
title_sort sulforaphane delays intervertebral disc degeneration by alleviating endoplasmic reticulum stress in nucleus pulposus cells via activating nrf-2/ho-1
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9840554/
https://www.ncbi.nlm.nih.gov/pubmed/36647429
http://dx.doi.org/10.1155/2023/3626091
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