title: Effects of manganese and arsenic species on the level of energy related nucleotides in human cells.
abstract: Cellular adenine and pyridine nucleotides play important roles in the cellular energy and redox state. An imbalance in the cellular levels of these tightly regulated energy related nucleotides can lead to oxidative stress and thus is discussed to contribute to neurotoxic and carcinogenic processes. Here we established a reliable ion-pair reversed phase HPLC based method for the parallel quantification of six energy related nucleotides (ATP, ADP, ADP-ribose, AMP, NAD(+), NADH) in cells and subsequently applied it to determine effects of manganese and arsenic species in cultured human cells. In human lung cells, MnCl(2) (≥50 μM) decreased the levels of ATP, NAD(+) and NADH as well as the NAD(+)/NADH ratio. This reflects a decline in the cellular energy metabolism, most likely resulting from a disturbance of the mitochondrial function. In contrast, cultured astrocytes were more resistant towards manganese. Regarding the arsenicals, a disturbance of the cellular energy related nucleotides was detected in lung cells for arsenite (≥50 μM), monomethylarsonous (≥1 μM), dimethylarsinous (≥1 μM) and dimethylarsinic acid (≥100 μM). Thereby, the single arsenicals seem to disturb the cellular energy and redox state by different mechanisms. Taken together, this study provides further evidence that cellular energy related nucleotides serve as sensitive indicators for toxic species exposure. When searching for a molecular mechanism of toxic compounds, the data illustrate the necessity of quantifying several energy related nucleotides in parallel, especially since ATP depletion, redox state alterations and oxidative stress are known to potentiate each other.
authors.affiliation: Graduate School of Chemistry, Wilhelm-Klemm-Str. 10, 48149 Münster, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Bornhorst
authors.forename: Franziska
authors.initials: F
authors.lastname: Ebert
authors.forename: Hanna
authors.initials: H
authors.lastname: Lohren
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Humpf
authors.forename: Uwe
authors.initials: U
authors.lastname: Karst
authors.forename: Tanja
authors.initials: T
authors.lastname: Schwerdtle
mesh_terms: D001151:Arsenic / Q000633:toxicity*; D018053:Arsenites / Q000633:toxicity; D002101:Cacodylic Acid / Q000031:analogs & derivatives / Q000633:toxicity; D045744:Cell Line, Tumor; D004734:Energy Metabolism / Q000187:drug effects*; D006801:Humans; D008345:Manganese / Q000633:toxicity*; D009711:Nucleotides / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects
chemical_list: D018053:Arsenites; D009711:Nucleotides; C472511:dimethylarsinous acid; D008345:Manganese; D002101:Cacodylic Acid; C015001:arsenite; D001151:Arsenic