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Tripartite motif 25 ameliorates doxorubicin-induced cardiotoxicity by degrading p85α
Doxorubicin (DOX)-based chemotherapy is widely used to treat malignant tumors; however, the cardiotoxicity induced by DOX restricts its clinical usage. A therapeutic dose of DOX can activate ubiquitin-proteasome system. However, whether and how ubiquitin-proteasome system brings out DOX-induced card...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9308790/ https://www.ncbi.nlm.nih.gov/pubmed/35871160 http://dx.doi.org/10.1038/s41419-022-05100-4 |
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author | Shen, Yihui Zhang, Hui Ni, Yangyue Wang, Xuejun Chen, Yifan Chen, Jiahui Wang, Yan Lin, Jinyi Xu, Yuchen Zhao, Jian-Yuan Cheng, Leilei |
author_facet | Shen, Yihui Zhang, Hui Ni, Yangyue Wang, Xuejun Chen, Yifan Chen, Jiahui Wang, Yan Lin, Jinyi Xu, Yuchen Zhao, Jian-Yuan Cheng, Leilei |
author_sort | Shen, Yihui |
collection | PubMed |
description | Doxorubicin (DOX)-based chemotherapy is widely used to treat malignant tumors; however, the cardiotoxicity induced by DOX restricts its clinical usage. A therapeutic dose of DOX can activate ubiquitin-proteasome system. However, whether and how ubiquitin-proteasome system brings out DOX-induced cardiotoxicity remains to be investigated. Here we conducted a proteomics analysis of a DOX-induced cardiotoxicity model to screen the potentially ubiquitination-related molecules. Dysregulated TRIM25 was found to contribute to the cardiotoxicity. In vivo and in vitro cardiotoxicity experiments revealed that TRIM25 ameliorated DOX-induced cardiotoxicity. Electron microscopy and endoplasmic reticulum stress markers revealed that TRIM25 mitigated endoplasmic reticulum stress and apoptosis in DOX-induced cardiomyocytes. Mechanistically, the Co-immunoprecipitation assays and CHX pulse-chase experiment determined that TRIM25 affected p85α stability and promoted its ubiquitination and degradation. This leads to increase of nuclear translocation of XBP-1s, which mitigates endoplasmic reticulum stress. These findings reveal that TRIM25 may have a therapeutic role for DOX-induced cardiotoxicity. |
format | Online Article Text |
id | pubmed-9308790 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-93087902022-07-25 Tripartite motif 25 ameliorates doxorubicin-induced cardiotoxicity by degrading p85α Shen, Yihui Zhang, Hui Ni, Yangyue Wang, Xuejun Chen, Yifan Chen, Jiahui Wang, Yan Lin, Jinyi Xu, Yuchen Zhao, Jian-Yuan Cheng, Leilei Cell Death Dis Article Doxorubicin (DOX)-based chemotherapy is widely used to treat malignant tumors; however, the cardiotoxicity induced by DOX restricts its clinical usage. A therapeutic dose of DOX can activate ubiquitin-proteasome system. However, whether and how ubiquitin-proteasome system brings out DOX-induced cardiotoxicity remains to be investigated. Here we conducted a proteomics analysis of a DOX-induced cardiotoxicity model to screen the potentially ubiquitination-related molecules. Dysregulated TRIM25 was found to contribute to the cardiotoxicity. In vivo and in vitro cardiotoxicity experiments revealed that TRIM25 ameliorated DOX-induced cardiotoxicity. Electron microscopy and endoplasmic reticulum stress markers revealed that TRIM25 mitigated endoplasmic reticulum stress and apoptosis in DOX-induced cardiomyocytes. Mechanistically, the Co-immunoprecipitation assays and CHX pulse-chase experiment determined that TRIM25 affected p85α stability and promoted its ubiquitination and degradation. This leads to increase of nuclear translocation of XBP-1s, which mitigates endoplasmic reticulum stress. These findings reveal that TRIM25 may have a therapeutic role for DOX-induced cardiotoxicity. Nature Publishing Group UK 2022-07-23 /pmc/articles/PMC9308790/ /pubmed/35871160 http://dx.doi.org/10.1038/s41419-022-05100-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Shen, Yihui Zhang, Hui Ni, Yangyue Wang, Xuejun Chen, Yifan Chen, Jiahui Wang, Yan Lin, Jinyi Xu, Yuchen Zhao, Jian-Yuan Cheng, Leilei Tripartite motif 25 ameliorates doxorubicin-induced cardiotoxicity by degrading p85α |
title | Tripartite motif 25 ameliorates doxorubicin-induced cardiotoxicity by degrading p85α |
title_full | Tripartite motif 25 ameliorates doxorubicin-induced cardiotoxicity by degrading p85α |
title_fullStr | Tripartite motif 25 ameliorates doxorubicin-induced cardiotoxicity by degrading p85α |
title_full_unstemmed | Tripartite motif 25 ameliorates doxorubicin-induced cardiotoxicity by degrading p85α |
title_short | Tripartite motif 25 ameliorates doxorubicin-induced cardiotoxicity by degrading p85α |
title_sort | tripartite motif 25 ameliorates doxorubicin-induced cardiotoxicity by degrading p85α |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9308790/ https://www.ncbi.nlm.nih.gov/pubmed/35871160 http://dx.doi.org/10.1038/s41419-022-05100-4 |
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