Skip Navigation


Carcinogenesis Advance Access originally published online on May 29, 2008
Carcinogenesis 2008 29(8):1528-1537; doi:10.1093/carcin/bgn125
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Data
Right arrow All Versions of this Article:
29/8/1528    most recent
bgn125v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Hervouet, E.
Right arrow Articles by Houstek, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hervouet, E.
Right arrow Articles by Houstek, J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

HIF and reactive oxygen species regulate oxidative phosphorylation in cancer

Eric Hervouet1,6,{dagger}, Alena Cízková2,3,{dagger}, Jocelyne Demont1, Alena Vojtísková2, Petr Pecina2, Nicole L.W. Franssen-van Hal5, Jaap Keijer5, Hélène Simonnet1,7, Robert Ivánek3,4, Stanislav Kmoch3, Catherine Godinot1,* and Josef Houstek2

1 Centre de Génétique Moléculaire et Cellulaire, UMR 5534, Centre National de la Recherche Scientifique, Claude Bernard University of Lyon 1, 43 Boulevard du onze novembre, 69622 Villeurbanne, Cedex, France
2 Institute of Physiology, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Praha, Czech Republic
3 Institute of Inherited Metabolic Disorders, Faculty of Medicine, Charles University, Ke Karlovu 2, Prague 12808, Czech Republic
4 Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Praha, Czech Republic
5 RIKILT—Institute of Food Safety, Wageningen, The Netherlands
6 Present address: Institut National de la Santé et de Recherche Médicale U601, Institute of Biology, 9 quai Moncousu, F-44035 Nantes, France
7 Present address: UMR 5201, Centre National de la Recherche Scientifique, Université Claude Bernard Lyon 1, F-69373 Lyon, France

* To whom correspondence should be addressed. Tel: +33 478364192; Fax: +33 4 72 43 26 85; Email: godinot1{at}yahoo.com

A decrease in oxidative phosphorylation (OXPHOS) is characteristic of many cancer types and, in particular, of clear cell renal carcinoma (CCRC) deficient in von Hippel–Lindau (vhl) gene. In the absence of functional pVHL, hypoxia-inducible factor (HIF) 1-{alpha} and HIF2-{alpha} subunits are stabilized, which induces the transcription of many genes including those involved in glycolysis and reactive oxygen species (ROS) metabolism. Transfection of these cells with vhl is known to restore HIF-{alpha} subunit degradation and to reduce glycolytic genes transcription. We show that such transfection with vhl of 786-0 CCRC (which are devoid of HIF1-{alpha}) also increased the content of respiratory chain subunits. However, the levels of most transcripts encoding OXPHOS subunits were not modified. Inhibition of HIF2-{alpha} synthesis by RNA interference in pVHL-deficient 786-0 CCRC also restored respiratory chain subunit content and clearly demonstrated a key role of HIF in OXPHOS regulation. In agreement with these observations, stabilization of HIF-{alpha} subunit by CoCl2 decreased respiratory chain subunit levels in CCRC cells expressing pVHL. In addition, HIF stimulated ROS production and mitochondrial manganese superoxide dismutase content. OXPHOS subunit content was also decreased by added H2O2. Interestingly, desferrioxamine (DFO) that also stabilized HIF did not decrease respiratory chain subunit level. While CoCl2 significantly stimulates ROS production, DFO is known to prevent hydroxyl radical production by inhibiting Fenton reactions. This indicates that the HIF-induced decrease in OXPHOS is at least in part mediated by hydroxyl radical production.

Abbreviations: CCRC, clear cell renal carcinoma; DCF, 2',7'-dichlorofluorescein; DFO, desferrioxamine; DMEM, Dulbecco’s modified Eagle’s medium; HIF, hypoxia-inducible factor; Mn-SOD, manganese superoxide dismutase; mRNA, messenger RNA; OXPHOS, oxidative phosphorylation; PCR, polymerase chain reaction; RCC, renal cancer cell; ROS, reactive oxygen species; SOD, superoxide dismutase; siRNA, small interfering RNA; vhl, von Hippel–Lindau

{dagger} These authors contributed equally to this work.

Received December 29, 2007; revised April 26, 2008; accepted May 14, 2008.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.