title: Arsenic exposure induces the Warburg effect in cultured human cells.
abstract: Understanding how arsenic exacts its diverse, global disease burden is hampered by a limited understanding of the particular biological pathways that are disrupted by arsenic and underlie pathogenesis. A reductionist view would predict that a small number of basic pathways are generally perturbed by arsenic, and manifest as diverse diseases. Following an initial observation that arsenite-exposed cells in culture acidify their media more rapidly than control cells, the report here shows that low level exposure to arsenite (75ppb) is sufficient to induce aerobic glycolysis (the Warburg effect) as a generalized phenomenon in cultured human primary cells and cell lines. Expanded studies in one such cell line, the non-malignant pulmonary epithelial line, BEAS-2B, established that the arsenite-induced Warburg effect was associated with increased accumulation of intracellular and extracellular lactate, an increased rate of extracellular acidification, and inhibition by the non-metabolized glucose analog, 2-deoxy-D-glucose. Associated with the induction of aerobic glycolysis was a pathway-wide induction of glycolysis gene expression, as well as protein accumulation of an established glycolysis master-regulator, hypoxia-inducible factor 1A. Arsenite-induced alteration of energy production in human cells represents the type of fundamental perturbation that could extend to many tissue targets and diseases.
authors: Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ 85724, USA.
authors: Fei
authors: F
authors: Zhao
authors: Paul
authors: P
authors: Severson
authors: Samantha
authors: S
authors: Pacheco
authors: Bernard W
authors: BW
authors: Futscher
authors: Walter T
authors: WT
authors: Klimecki
mesh_terms: D018053:Arsenites / Q000633:toxicity*; D002460:Cell Line; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism; D019344:Lactic Acid; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017670:Sodium Compounds / Q000633:toxicity*
chemical_list: D018053:Arsenites; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017670:Sodium Compounds; D019344:Lactic Acid; C017947:sodium arsenite; D003847:Deoxyglucose
keywords: 2-DG; 2-Deoxy-d-glucose; Arsenite; As; Glycolysis; HIF-1A; Hypoxia inducible factor-1 alpha subunit; Hypoxia-inducible factor 1; Warburg effect
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