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Berberine alleviates ox-LDL induced inflammatory factors by up-regulation of autophagy via AMPK/mTOR signaling pathway
BACKGROUND: Inflammation induced by oxidized low-density lipoprotein (ox-LDL) plays an important role in the pathogenesis of atherosclerosis. Recently, roles of autophagy against inflammation in the process of atherosclerosis have drawn increasing attention. Here, we tested the possible molecular me...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4365560/ https://www.ncbi.nlm.nih.gov/pubmed/25884210 http://dx.doi.org/10.1186/s12967-015-0450-z |
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author | Fan, Xiaodi Wang, Jun Hou, Jincai Lin, Chengren Bensoussan, Alan Chang, Dennis Liu, Jianxun Wang, Bing |
author_facet | Fan, Xiaodi Wang, Jun Hou, Jincai Lin, Chengren Bensoussan, Alan Chang, Dennis Liu, Jianxun Wang, Bing |
author_sort | Fan, Xiaodi |
collection | PubMed |
description | BACKGROUND: Inflammation induced by oxidized low-density lipoprotein (ox-LDL) plays an important role in the pathogenesis of atherosclerosis. Recently, roles of autophagy against inflammation in the process of atherosclerosis have drawn increasing attention. Here, we tested the possible molecular mechanisms by which berberine confers an anti-inflammatory effect in macrophages by upregulation of autophagy. METHODS: J774A.1 macrophages were incubated with various doses of ox-LDL for various times. We evaluated the inflammatory factors and autophagy proteins (LC3II/LC3I, and SQSTM1/p62) to ascertain the optimal dose and time. Ox-LDL–induced inflammatory factors and autophagy in J774A.1 cells were tested by the AimPlex multiplex assay, Western blotting, confocal microscopy, and transmission electron microscopy in the presence of berberine or chloroquine (CQ). Adenosine 5’-monophosphate-activated protein kinase (AMPK) inhibitor compound C was used to evaluate the AMPK/mTOR signaling pathway. RESULTS: Berberine dose- and time-dependently reduced ox-LDL–induced inflammation and increased the ratio of LC3II/LC3I, and SQSTM1/p62 in J774A.1 cells. CQ significantly attenuated the berberine-induced autophagy and anti-inflammation. In addition, berberine increased the ratio of p-AMPK/AMPK and decreased the ratio of p-mTOR/mTOR. AMPK inhibitor compound C abolished berberine-induced autophagy and promoted p-mTOR/mTOR expression in J774A.1 cells. CONCLUSION: Berberine treatment inhibits inflammation in J774A.1 cells by inducing autophagy, which is mediated through activation of the AMPK/mTOR signaling pathway. Importantly, this study provides new insight into berberine’s molecular mechanism and its therapeutic potential in the treatment of atherosclerosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-015-0450-z) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4365560 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-43655602015-03-20 Berberine alleviates ox-LDL induced inflammatory factors by up-regulation of autophagy via AMPK/mTOR signaling pathway Fan, Xiaodi Wang, Jun Hou, Jincai Lin, Chengren Bensoussan, Alan Chang, Dennis Liu, Jianxun Wang, Bing J Transl Med Research BACKGROUND: Inflammation induced by oxidized low-density lipoprotein (ox-LDL) plays an important role in the pathogenesis of atherosclerosis. Recently, roles of autophagy against inflammation in the process of atherosclerosis have drawn increasing attention. Here, we tested the possible molecular mechanisms by which berberine confers an anti-inflammatory effect in macrophages by upregulation of autophagy. METHODS: J774A.1 macrophages were incubated with various doses of ox-LDL for various times. We evaluated the inflammatory factors and autophagy proteins (LC3II/LC3I, and SQSTM1/p62) to ascertain the optimal dose and time. Ox-LDL–induced inflammatory factors and autophagy in J774A.1 cells were tested by the AimPlex multiplex assay, Western blotting, confocal microscopy, and transmission electron microscopy in the presence of berberine or chloroquine (CQ). Adenosine 5’-monophosphate-activated protein kinase (AMPK) inhibitor compound C was used to evaluate the AMPK/mTOR signaling pathway. RESULTS: Berberine dose- and time-dependently reduced ox-LDL–induced inflammation and increased the ratio of LC3II/LC3I, and SQSTM1/p62 in J774A.1 cells. CQ significantly attenuated the berberine-induced autophagy and anti-inflammation. In addition, berberine increased the ratio of p-AMPK/AMPK and decreased the ratio of p-mTOR/mTOR. AMPK inhibitor compound C abolished berberine-induced autophagy and promoted p-mTOR/mTOR expression in J774A.1 cells. CONCLUSION: Berberine treatment inhibits inflammation in J774A.1 cells by inducing autophagy, which is mediated through activation of the AMPK/mTOR signaling pathway. Importantly, this study provides new insight into berberine’s molecular mechanism and its therapeutic potential in the treatment of atherosclerosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-015-0450-z) contains supplementary material, which is available to authorized users. BioMed Central 2015-03-15 /pmc/articles/PMC4365560/ /pubmed/25884210 http://dx.doi.org/10.1186/s12967-015-0450-z Text en © Fan et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Fan, Xiaodi Wang, Jun Hou, Jincai Lin, Chengren Bensoussan, Alan Chang, Dennis Liu, Jianxun Wang, Bing Berberine alleviates ox-LDL induced inflammatory factors by up-regulation of autophagy via AMPK/mTOR signaling pathway |
title | Berberine alleviates ox-LDL induced inflammatory factors by up-regulation of autophagy via AMPK/mTOR signaling pathway |
title_full | Berberine alleviates ox-LDL induced inflammatory factors by up-regulation of autophagy via AMPK/mTOR signaling pathway |
title_fullStr | Berberine alleviates ox-LDL induced inflammatory factors by up-regulation of autophagy via AMPK/mTOR signaling pathway |
title_full_unstemmed | Berberine alleviates ox-LDL induced inflammatory factors by up-regulation of autophagy via AMPK/mTOR signaling pathway |
title_short | Berberine alleviates ox-LDL induced inflammatory factors by up-regulation of autophagy via AMPK/mTOR signaling pathway |
title_sort | berberine alleviates ox-ldl induced inflammatory factors by up-regulation of autophagy via ampk/mtor signaling pathway |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4365560/ https://www.ncbi.nlm.nih.gov/pubmed/25884210 http://dx.doi.org/10.1186/s12967-015-0450-z |
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