title: Zinc has ambiguous effects on chromium (VI)-induced oxidative stress and apoptosis.
abstract: Zinc is an important cellular antioxidant. We investigated its role in chromium-induced oxidative stress and apoptosis in human tumor cell line Hep-2. The measured parameters included intracellular labile zinc content (Zinquin-E fluorescence), cell viability (WST-1 assay), oxidative stress (spectrophotometry), mitochondrial potential (flow cytometry), caspase-3 activity, and PARP cleavage (immunofluorescence). We found that Hep-2 cells contain abundant labile zinc stores that may be depleted by the ionophore TPEN or increased by external zinc supplementation. Chromium (VI)-induced cytotoxicity and apoptosis were enhanced in zinc-depleted cells after 24 h, in particular at chromium (VI) concentrations of 50 and 150 micromol/l. On the other hand, elevated levels of labile zinc were able to protect against apoptosis induced by 10 micromol/l chromium (VI) but at higher chromium (VI) concentrations (50 and 150 micromol/l) acted synergistically, significantly enhancing oxidative stress and the course of apoptosis, possibly through oxidative stress and mitochondrial damage.
authors.affiliation: Department of Medical Biology and Genetics, Faculty of Medicine, Charles University Prague, Simkova 870, 500 38 Hradec Krdlove, Czech Republic. rudolf@lfhk.cuni.cz
authors.forename: Emil
authors.initials: E
authors.lastname: Rudolf
authors.forename: Miroslav
authors.initials: M
authors.lastname: Cervinka
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Cerman
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002840:Chromates / Q000494:pharmacology; D004789:Enzyme Activation; D005456:Fluorescent Dyes; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017680:Potassium Compounds / Q000494:pharmacology; D015363:Quinolones; D014105:Tosyl Compounds; D015032:Zinc / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D002840:Chromates; D005456:Fluorescent Dyes; D017680:Potassium Compounds; D015363:Quinolones; D014105:Tosyl Compounds; C027373:potassium chromate(VI); D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D015032:Zinc; C084731:zinquin