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Proteomic approach for understanding milder neurotoxicity of Carfilzomib against Bortezomib
The proteasomal system is responsible for the turnover of damaged proteins. Because of its important functions in oncogenesis, inhibiting the proteasomal system is a promising therapeutic approach for cancer treatment. Bortezomib (BTZ) is the first proteasome inhibitor approved by FDA for clinical a...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218500/ https://www.ncbi.nlm.nih.gov/pubmed/30397214 http://dx.doi.org/10.1038/s41598-018-34507-3 |
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author | Karademir, Betul Sari, Gulce Jannuzzi, Ayse Tarbin Musunuri, Sravani Wicher, Grzegorz Grune, Tilman Mi, Jia Hacioglu-Bay, Husniye Forsberg-Nilsson, Karin Bergquist, Jonas Jung, Tobias |
author_facet | Karademir, Betul Sari, Gulce Jannuzzi, Ayse Tarbin Musunuri, Sravani Wicher, Grzegorz Grune, Tilman Mi, Jia Hacioglu-Bay, Husniye Forsberg-Nilsson, Karin Bergquist, Jonas Jung, Tobias |
author_sort | Karademir, Betul |
collection | PubMed |
description | The proteasomal system is responsible for the turnover of damaged proteins. Because of its important functions in oncogenesis, inhibiting the proteasomal system is a promising therapeutic approach for cancer treatment. Bortezomib (BTZ) is the first proteasome inhibitor approved by FDA for clinical applications. However neuropathic side effects are dose limiting for BTZ as many other chemotherapeutic agents. Therefore second-generation proteasome inhibitors have been developed including carfilzomib (CFZ). Aim of the present work was investigating the mechanisms of peripheral neuropathy triggered by the proteasome inhibitor BTZ and comparing the pathways affected by BTZ and CFZ, respectively. Neural stem cells, isolated from the cortex of E14 mouse embryos, were treated with BTZ and CFZ and mass spectrometry was used to compare the global protein pool of treated cells. BTZ was shown to cause more severe cytoskeletal damage, which is crucial in neural cell integrity. Excessive protein carbonylation and actin filament destabilization were also detected following BTZ treatment that was lower following CFZ treatment. Our data on cytoskeletal proteins, chaperone system, and protein oxidation may explain the milder neurotoxic effects of CFZ in clinical applications. |
format | Online Article Text |
id | pubmed-6218500 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-62185002018-11-07 Proteomic approach for understanding milder neurotoxicity of Carfilzomib against Bortezomib Karademir, Betul Sari, Gulce Jannuzzi, Ayse Tarbin Musunuri, Sravani Wicher, Grzegorz Grune, Tilman Mi, Jia Hacioglu-Bay, Husniye Forsberg-Nilsson, Karin Bergquist, Jonas Jung, Tobias Sci Rep Article The proteasomal system is responsible for the turnover of damaged proteins. Because of its important functions in oncogenesis, inhibiting the proteasomal system is a promising therapeutic approach for cancer treatment. Bortezomib (BTZ) is the first proteasome inhibitor approved by FDA for clinical applications. However neuropathic side effects are dose limiting for BTZ as many other chemotherapeutic agents. Therefore second-generation proteasome inhibitors have been developed including carfilzomib (CFZ). Aim of the present work was investigating the mechanisms of peripheral neuropathy triggered by the proteasome inhibitor BTZ and comparing the pathways affected by BTZ and CFZ, respectively. Neural stem cells, isolated from the cortex of E14 mouse embryos, were treated with BTZ and CFZ and mass spectrometry was used to compare the global protein pool of treated cells. BTZ was shown to cause more severe cytoskeletal damage, which is crucial in neural cell integrity. Excessive protein carbonylation and actin filament destabilization were also detected following BTZ treatment that was lower following CFZ treatment. Our data on cytoskeletal proteins, chaperone system, and protein oxidation may explain the milder neurotoxic effects of CFZ in clinical applications. Nature Publishing Group UK 2018-11-05 /pmc/articles/PMC6218500/ /pubmed/30397214 http://dx.doi.org/10.1038/s41598-018-34507-3 Text en © The Author(s) 2018 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/. |
spellingShingle | Article Karademir, Betul Sari, Gulce Jannuzzi, Ayse Tarbin Musunuri, Sravani Wicher, Grzegorz Grune, Tilman Mi, Jia Hacioglu-Bay, Husniye Forsberg-Nilsson, Karin Bergquist, Jonas Jung, Tobias Proteomic approach for understanding milder neurotoxicity of Carfilzomib against Bortezomib |
title | Proteomic approach for understanding milder neurotoxicity of Carfilzomib against Bortezomib |
title_full | Proteomic approach for understanding milder neurotoxicity of Carfilzomib against Bortezomib |
title_fullStr | Proteomic approach for understanding milder neurotoxicity of Carfilzomib against Bortezomib |
title_full_unstemmed | Proteomic approach for understanding milder neurotoxicity of Carfilzomib against Bortezomib |
title_short | Proteomic approach for understanding milder neurotoxicity of Carfilzomib against Bortezomib |
title_sort | proteomic approach for understanding milder neurotoxicity of carfilzomib against bortezomib |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218500/ https://www.ncbi.nlm.nih.gov/pubmed/30397214 http://dx.doi.org/10.1038/s41598-018-34507-3 |
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