PMID- 20654728 OWN - NLM STAT- MEDLINE DCOM- 20110309 LR - 20191210 IS - 1878-5875 (Electronic) IS - 1357-2725 (Linking) VI - 42 IP - 10 DP - 2010 Oct TI - Oxidative phosphorylation is impaired by prolonged hypoxia in breast and possibly in cervix carcinoma. PG - 1744-51 LID - 10.1016/j.biocel.2010.07.010 [doi] AB - 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 8h (two times increased glycolysis-related mRNA synthesis promoted by increased HIF-1alpha levels). However, major metabolic remodeling was observed only after 24h hypoxia: increased glycolytic protein content (1-5-times), enzyme activities (2-times) and fluxes (4-6-times). Interestingly, in MCF-7 cells, 24h 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, 24h 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. CI - Copyright 2010 Elsevier Ltd. All rights reserved. FAU - Rodriguez-Enriquez, Sara AU - Rodriguez-Enriquez S AD - Departamento de Bioquimica, Instituto Nacional de Cardiologia Ignacio Chavez, Mexico DF, Mexico. saren960104@hotmail.com FAU - Carreno-Fuentes, Liliana AU - Carreno-Fuentes L FAU - Gallardo-Perez, Juan Carlos AU - Gallardo-Perez JC FAU - Saavedra, Emma AU - Saavedra E FAU - Quezada, Hector AU - Quezada H FAU - Vega, Alicia AU - Vega A FAU - Marin-Hernandez, Alvaro AU - Marin-Hernandez A FAU - Olin-Sandoval, Viridiana AU - Olin-Sandoval V FAU - Torres-Marquez, M Eugenia AU - Torres-Marquez ME FAU - Moreno-Sanchez, Rafael AU - Moreno-Sanchez R LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100721 PL - Netherlands TA - Int J Biochem Cell Biol JT - The international journal of biochemistry & cell biology JID - 9508482 RN - 0 (HIF1A protein, human) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - EC 1.2.4.2 (Ketoglutarate Dehydrogenase Complex) RN - EC 3.5.1.2 (Glutaminase) RN - EC 7.1.1.2 (Electron Transport Complex I) SB - IM MH - Breast Neoplasms/*metabolism/pathology MH - Carcinoma/*metabolism/pathology MH - Electron Transport Complex I/metabolism MH - Energy Metabolism MH - Female MH - Glutaminase/genetics/metabolism MH - Glycolysis MH - HeLa Cells MH - Humans MH - Hypoxia/*metabolism MH - Hypoxia-Inducible Factor 1, alpha Subunit/biosynthesis/genetics MH - Ketoglutarate Dehydrogenase Complex/genetics/metabolism MH - Mitochondria/*metabolism MH - Oxidative Phosphorylation MH - Uterine Cervical Neoplasms/*metabolism/pathology EDAT- 2010/07/27 06:00 MHDA- 2011/03/10 06:00 CRDT- 2010/07/27 06:00 PHST- 2010/03/26 00:00 [received] PHST- 2010/06/18 00:00 [revised] PHST- 2010/07/12 00:00 [accepted] PHST- 2010/07/27 06:00 [entrez] PHST- 2010/07/27 06:00 [pubmed] PHST- 2011/03/10 06:00 [medline] AID - S1357-2725(10)00258-X [pii] AID - 10.1016/j.biocel.2010.07.010 [doi] PST - ppublish SO - Int J Biochem Cell Biol. 2010 Oct;42(10):1744-51. doi: 10.1016/j.biocel.2010.07.010. Epub 2010 Jul 21.