title: Short-term exposure of nontumorigenic human bronchial epithelial cells to carcinogenic chromium(VI) compromises their respiratory capacity and alters their bioenergetic signature.
abstract: Previous studies on the impact of hexavalent chromium [Cr(VI)] on mammalian cell energetics revealed alterations suggestive of a shift to a more fermentative metabolism. Aiming at a more defined understanding of the metabolic effects of Cr(VI) and of their molecular basis, we assessed the impact of a mild Cr(VI) exposure on critical bioenergetic parameters (lactate production, oxygen consumption and intracellular ATP levels). Cells derived from normal human bronchial epithelium (BEAS-2B cell line), the main in vivo target of Cr(VI) carcinogenicity, were subjected for 48 h to 1 μM Cr(VI). We could confirm a shift to a more fermentative metabolism, resulting from the simultaneous inhibition of respiration and stimulation of glycolysis. This shift was accompanied by a decrease in the protein levels of the catalytic subunit (subunit β) of the mitochondrial H(+)-ATP synthase (β-F1-ATPase) and a concomitant marked increase in those of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The corresponding alteration in the β-F1-ATPase/GAPDH protein ratio (viewed as a bioenergetic signature) upon Cr(VI) exposure was in agreement with the observed attenuation of cellular respiration and enhancement of glycolytic flux. Altogether, these results constitute a novel finding in terms of the molecular mechanisms of Cr(VI) effects.
authors.affiliation: Unidade de Química-Física Molecular and Departamento de Ciências da Vida, Universidade de Coimbra, 3000-456 Coimbra, Portugal ; Centro de Biología Molecular "Severo Ochoa", CIBERER, Instituto de Investigación Hospital 12 de Octubre, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: Joana F
authors.initials: JF
authors.lastname: Cerveira
authors.affiliation: Centro de Biología Molecular "Severo Ochoa", CIBERER, Instituto de Investigación Hospital 12 de Octubre, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Sánchez-Aragó
authors.affiliation: Unidade de Química-Física Molecular and Departamento de Ciências da Vida, Universidade de Coimbra, 3000-456 Coimbra, Portugal ; Centro de Investigação em Meio Ambiente, Genética e Oncobiologia (CIMAGO), Universidade de Coimbra, 3004-504 Coimbra, Portugal.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Urbano
authors.affiliation: Centro de Biología Molecular "Severo Ochoa", CIBERER, Instituto de Investigación Hospital 12 de Octubre, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Cuezva
keywords: 2,4-DNP, 2,4-dinitrophenol; 2-DG, 2-deoxyglucose; Aerobic glycolysis; Cellular bioenergetic index; Cellular energy status; Cellular respiration; Chromate lung cancer; Cr(III), trivalent chromium; Cr(IV), tetravalent chromium; Cr(V), pentavalent chromium; Cr(VI), hexavalent chromium; DCF, 2′,7′-dichlorofluorescein; EDTA, ethylenediaminetetracetic acid; ETC, mitochondrial electron transport chain; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; IARC, International Agency for Research on Cancer; OCR, oxygen consumption rate; OXPHOS, oxidative phosphorylation; PBS, phosphate-buffered saline; PI, propidium iodide; ROS, reactive oxygen species; TCA, tricarboxylic acid; Warburg effect; β-F1-ATPase, catalytic subunit (subunit β) of the mitochondrial H+-ATP synthase