title: Toxic effects of Cr(VI) and Cr(III) on energy metabolism of heterotrophic Euglena gracilis.
abstract: To assess the toxic effect of Cr on energy metabolism, heterotrophic Euglena gracilis was grown in a medium that prompts high yield biomass and in the presence of different Cr(VI) or Cr(III) concentrations. The cell growth IC₅₀ value was 12 and >250μM for Cr(VI) and Cr(III), respectively; in these cells chromium was accumulated and a fraction compartmentalized into mitochondria, and synthesis of cysteine and glutathione was induced. Respiration of control isolated mitochondria was strongly inhibited by added Cr(VI) or Cr(III) with L-lactate or succinate as substrates. In turn, cellular and mitochondrial respiration, respiratory Complexes I, III and IV, glycolysis and cytosolic NAD(+)-alcohol and -lactate dehydrogenases from cells cultured with Cr(VI) were significantly lower than control, whereas AOX and external NADH dehydrogenase activities were unaltered or increased, respectively. Addition of Cr(VI) or Cr(III) to isolated mitochondria or cytosol from control- or Cr(VI)-grown cells induced inhibition of respiration, respiratory Complexes III, IV and AOX, and glycolytic pyruvate kinase; whereas Complex I, external NADH dehydrogenase, and other glycolytic enzymes were unaffected. Protein contents of mitochondrial Complexes I, III, IV and V, and ANT were diminished in Cr(VI)-grown cells. Decreased respiration and glycolysis induced by Cr(VI) resulted in lower cellular ATP content. Results suggested that Cr(VI) cytotoxicity altered gene expression (as widely documented) and hence enzyme content, and induced oxidative stress, but it was also related with direct enzyme inhibition; Cr(III) was also cytotoxic although at higher concentrations. These findings establish new paradigms for chromium toxicity: Cr(VI) direct enzyme inhibition and non-innocuous external Cr(III) toxicity.
authors.affiliation: Departamento de Bioquímica, Instituto Nacional de Cardiología, Tlalpan, México D.F., Mexico. rjass_cardiol@yahoo.com.mx
authors.forename: Ricardo
authors.initials: R
authors.lastname: Jasso-Chávez
authors.forename: Angélica
authors.initials: A
authors.lastname: Pacheco-Rosales
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Lira-Silva
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Gallardo-Pérez
authors.forename: Noemí
authors.initials: N
authors.lastname: García
authors.forename: Rafael
authors.initials: R
authors.lastname: Moreno-Sánchez
mesh_terms: D000818:Animals; D002244:Carbon / Q000378:metabolism; D049108:Cell Enlargement / Q000187:drug effects; D002857:Chromium / Q000378:metabolism / Q000633:toxicity*; D004734:Energy Metabolism / Q000187:drug effects*; D004785:Environmental Pollutants / Q000633:toxicity*; D005056:Euglena gracilis / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D005936:Glucans / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D052836:Heterotrophic Processes; D008315:Malondialdehyde / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology
chemical_list: D004785:Environmental Pollutants; D005936:Glucans; D002857:Chromium; C074702:chromium hexavalent ion; D008315:Malondialdehyde; C003045:paramylon; D002244:Carbon