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Hypoxia Strongly Affects Mitochondrial Ribosomal Proteins and Translocases, as Shown by Quantitative Proteomics of HeLa Cells

Hypoxia is an important and common characteristic of many human tumors. It is a challenge clinically due to the correlation with poor prognosis and resistance to radiation and chemotherapy. Understanding the biochemical response to hypoxia would facilitate the development of novel therapeutics for c...

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Autores principales: Bousquet, Paula A., Sandvik, Joe Alexander, Arntzen, Magnus Ø., Jeppesen Edin, Nina F., Christoffersen, Stine, Krengel, Ute, Pettersen, Erik O., Thiede, Bernd
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4572459/
https://www.ncbi.nlm.nih.gov/pubmed/26421188
http://dx.doi.org/10.1155/2015/678527
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author Bousquet, Paula A.
Sandvik, Joe Alexander
Arntzen, Magnus Ø.
Jeppesen Edin, Nina F.
Christoffersen, Stine
Krengel, Ute
Pettersen, Erik O.
Thiede, Bernd
author_facet Bousquet, Paula A.
Sandvik, Joe Alexander
Arntzen, Magnus Ø.
Jeppesen Edin, Nina F.
Christoffersen, Stine
Krengel, Ute
Pettersen, Erik O.
Thiede, Bernd
author_sort Bousquet, Paula A.
collection PubMed
description Hypoxia is an important and common characteristic of many human tumors. It is a challenge clinically due to the correlation with poor prognosis and resistance to radiation and chemotherapy. Understanding the biochemical response to hypoxia would facilitate the development of novel therapeutics for cancer treatment. Here, we investigate alterations in gene expression in response to hypoxia by quantitative proteome analysis using stable isotope labeling with amino acids in cell culture (SILAC) in conjunction with LCMS/MS. Human HeLa cells were kept either in a hypoxic environment or under normoxic conditions. 125 proteins were found to be regulated, with maximum alteration of 18-fold. In particular, three clusters of differentially regulated proteins were identified, showing significant upregulation of glycolysis and downregulation of mitochondrial ribosomal proteins and translocases. This interaction is likely orchestrated by HIF-1. We also investigated the effect of hypoxia on the cell cycle, which shows accumulation in G1 and a prolonged S phase under these conditions. Implications. This work not only improves our understanding of the response to hypoxia, but also reveals proteins important for malignant progression, which may be targeted in future therapies.
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spelling pubmed-45724592015-09-29 Hypoxia Strongly Affects Mitochondrial Ribosomal Proteins and Translocases, as Shown by Quantitative Proteomics of HeLa Cells Bousquet, Paula A. Sandvik, Joe Alexander Arntzen, Magnus Ø. Jeppesen Edin, Nina F. Christoffersen, Stine Krengel, Ute Pettersen, Erik O. Thiede, Bernd Int J Proteomics Research Article Hypoxia is an important and common characteristic of many human tumors. It is a challenge clinically due to the correlation with poor prognosis and resistance to radiation and chemotherapy. Understanding the biochemical response to hypoxia would facilitate the development of novel therapeutics for cancer treatment. Here, we investigate alterations in gene expression in response to hypoxia by quantitative proteome analysis using stable isotope labeling with amino acids in cell culture (SILAC) in conjunction with LCMS/MS. Human HeLa cells were kept either in a hypoxic environment or under normoxic conditions. 125 proteins were found to be regulated, with maximum alteration of 18-fold. In particular, three clusters of differentially regulated proteins were identified, showing significant upregulation of glycolysis and downregulation of mitochondrial ribosomal proteins and translocases. This interaction is likely orchestrated by HIF-1. We also investigated the effect of hypoxia on the cell cycle, which shows accumulation in G1 and a prolonged S phase under these conditions. Implications. This work not only improves our understanding of the response to hypoxia, but also reveals proteins important for malignant progression, which may be targeted in future therapies. Hindawi Publishing Corporation 2015 2015-09-02 /pmc/articles/PMC4572459/ /pubmed/26421188 http://dx.doi.org/10.1155/2015/678527 Text en Copyright © 2015 Paula A. Bousquet et al. https://creativecommons.org/licenses/by/3.0/ 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
Bousquet, Paula A.
Sandvik, Joe Alexander
Arntzen, Magnus Ø.
Jeppesen Edin, Nina F.
Christoffersen, Stine
Krengel, Ute
Pettersen, Erik O.
Thiede, Bernd
Hypoxia Strongly Affects Mitochondrial Ribosomal Proteins and Translocases, as Shown by Quantitative Proteomics of HeLa Cells
title Hypoxia Strongly Affects Mitochondrial Ribosomal Proteins and Translocases, as Shown by Quantitative Proteomics of HeLa Cells
title_full Hypoxia Strongly Affects Mitochondrial Ribosomal Proteins and Translocases, as Shown by Quantitative Proteomics of HeLa Cells
title_fullStr Hypoxia Strongly Affects Mitochondrial Ribosomal Proteins and Translocases, as Shown by Quantitative Proteomics of HeLa Cells
title_full_unstemmed Hypoxia Strongly Affects Mitochondrial Ribosomal Proteins and Translocases, as Shown by Quantitative Proteomics of HeLa Cells
title_short Hypoxia Strongly Affects Mitochondrial Ribosomal Proteins and Translocases, as Shown by Quantitative Proteomics of HeLa Cells
title_sort hypoxia strongly affects mitochondrial ribosomal proteins and translocases, as shown by quantitative proteomics of hela cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4572459/
https://www.ncbi.nlm.nih.gov/pubmed/26421188
http://dx.doi.org/10.1155/2015/678527
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