title: Hypoxia Strongly Affects Mitochondrial Ribosomal Proteins and Translocases, as Shown by Quantitative Proteomics of HeLa Cells.
abstract: 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.
authors.affiliation: Department of Chemistry, University of Oslo, P.O. Box 1033 Blindern, 0315 Oslo, Norway.
authors.forename: Paula A
authors.initials: PA
authors.lastname: Bousquet
authors.affiliation: Department of Physics, University of Oslo, P.O. Box 1048 Blindern, 0315 Oslo, Norway.
authors.forename: Joe Alexander
authors.initials: JA
authors.lastname: Sandvik
authors.affiliation: The Biotechnology Centre of Oslo, University of Oslo, P.O. Box 1125 Blindern, 0317 Oslo, Norway.
authors.forename: Magnus Ø
authors.initials: MØ
authors.lastname: Arntzen
authors.affiliation: Department of Physics, University of Oslo, P.O. Box 1048 Blindern, 0315 Oslo, Norway.
authors.forename: Nina F
authors.initials: NF
authors.lastname: Jeppesen Edin
authors.affiliation: Department of Physics, University of Oslo, P.O. Box 1048 Blindern, 0315 Oslo, Norway.
authors.forename: Stine
authors.initials: S
authors.lastname: Christoffersen
authors.affiliation: Department of Chemistry, University of Oslo, P.O. Box 1033 Blindern, 0315 Oslo, Norway.
authors.forename: Ute
authors.initials: U
authors.lastname: Krengel
authors.affiliation: Department of Physics, University of Oslo, P.O. Box 1048 Blindern, 0315 Oslo, Norway.
authors.forename: Erik O
authors.initials: EO
authors.lastname: Pettersen
authors.affiliation: The Biotechnology Centre of Oslo, University of Oslo, P.O. Box 1125 Blindern, 0317 Oslo, Norway ; Department of Biosciences, University of Oslo, P.O. Box 1066 Blindern, 0316 Oslo, Norway.
authors.forename: Bernd
authors.initials: B
authors.lastname: Thiede