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Oxidative phosphorylation is impaired by prolonged hypoxia in breast and possibly in cervix carcinoma

2010; Elsevier BV; Volume: 42; Issue: 10 Linguagem: Inglês

10.1016/j.biocel.2010.07.010

1878-5875

Sara Rodríguez‐Enríquez, Liliana Carreño‐Fuentes, Juan Carlos Gallardo‐Pérez, Emma Saavedra, Héctor Quezada, A. Vega, Álvaro Marín‐Hernández, Viridiana Olín‐Sandoval, M.Eugenia Torres-Márquez, Rafael Moreno‐Sánchez,

Adipose Tissue and Metabolism

It has been assumed that oxidative phosphorylation (OxPhos) in solid tumors is severely reduced due to cytochrome c oxidase substrate restriction, although the measured extracellular oxygen concentration in hypoxic areas seems not limiting for this activity. To identify alternative hypoxia-induced OxPhos depressing mechanisms, an integral analysis of transcription, translation, enzyme activities and pathway fluxes was performed on glycolysis and OxPhos in HeLa and MCF-7 carcinomas. In both neoplasias exposed to hypoxia, an early transcriptional response was observed after 8 h (two times increased glycolysis-related mRNA synthesis promoted by increased HIF-1α levels). However, major metabolic remodeling was observed only after 24 h hypoxia: increased glycolytic protein content (1–5-times), enzyme activities (2-times) and fluxes (4–6-times). Interestingly, in MCF-7 cells, 24 h hypoxia decreased OxPhos flux (4–6-fold), and 2-oxoglutarate dehydrogenase and glutaminase activities (3-fold), with no changes in respiratory complexes I and IV activities. In contrast, 24 h hypoxia did not significantly affect HeLa OxPhos flux; neither mitochondria related mRNAs, protein contents or enzyme activities, although the enhanced glycolysis became the main ATP supplier. Thus, prolonged hypoxia (a) targeted some mitochondrial enzymes in MCF-7 but not in HeLa cells, and (b) induced a transition from mitochondrial towards a glycolytic-dependent energy metabolism in both MCF-7 and HeLa carcinomas.