A targeted antioxidant reveals the importance of mitochondrial reactive oxygen species in the hypoxic signaling of HIF-1alpha.

TitleA targeted antioxidant reveals the importance of mitochondrial reactive oxygen species in the hypoxic signaling of HIF-1alpha.
Publication TypeJournal Article
Year of Publication2005
AuthorsSanjuan-Pla, A, Cervera, AM, Apostolova, N, Garcia-Bou, R, Víctor, VM, Murphy, MP, McCreath, KJ
JournalFEBS Lett
Volume579
Issue12
Pagination2669-74
Date Published2005 May 9
ISSN0014-5793
KeywordsAntioxidants, Blotting, Western, Cell Hypoxia, Cell Line, Tumor, Fibrosarcoma, Gene Expression, Gene Targeting, Genes, Reporter, Hepatoblastoma, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Luciferases, Mitochondria, Oxygen, Reactive Oxygen Species, Reverse Transcriptase Polymerase Chain Reaction, Time Factors, Transcription Factors
Abstract

Exposure to limiting oxygen in cells and tissues induce the stabilization and transcriptional activation of the hypoxia-inducible factor 1 alpha (HIF-1alpha) protein, a key regulator of the hypoxic response. Reactive oxygen species (ROS) generation has been implicated in the stabilization of HIF-1alpha during this response, but this is still a matter of some debate. In this study we utilize a mitochondria-targeted antioxidant, mitoubiquinone (MitoQ), and examine its effects on the hypoxic stabilization of HIF-1alpha. Our results show that under conditions of reduced oxygen (3% O(2)), MitoQ ablated the hypoxic induction of ROS generation and destabilized HIF-1alpha protein. This in turn led to an abrogation of HIF-1 transcriptional activity. Normoxic stabilization of HIF-1alpha, on the other hand, was unchanged in the presence of MitoQ suggesting that ROS were not involved. This study strongly suggests that mitochondrial ROS contribute to the hypoxic stabilization of HIF-1alpha.

DOI10.1016/j.febslet.2005.03.088
Alternate JournalFEBS Lett.
Citation Key10.1016/j.febslet.2005.03.088
PubMed ID15862307