Early response of glutathione- and thioredoxin-dependent antioxidant defense systems to Tl(I)- and Tl(III)-mediated oxidative stress in adherent pheochromocytoma (PC12adh) cells
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Thallium (Tl) is a toxic heavy metal that causes oxidative stress both in vitro and in vivo. In this work, we evaluated the production of oxygen (ROS)- and nitrogen (RNS)-reactive species in adherent PC12 (PC12adh) cells exposed for 0.5–6 h to Tl(I) or Tl(III) (10–100 µM). In this system, Tl(I) induced mostly H2O2 generation while Tl(III) induced H2O2 and ONOO·− generation. Both cations enhanced iNOS expression and activity, and decreased CuZnSOD expression but without affecting its activity. Tl(I) increased MnSOD expression and activity but Tl(III) decreased them. NADPH oxidase (NOX) activity remained unaffected throughout the period assessed. Oxidant levels returned to baseline values after 6 h of incubation, suggesting a response of the antioxidant defense system to the oxidative insult imposed by the cations. Tl also affected the glutathione-dependent system: while Tl(III) increased glutathione peroxidase (GPx) expression and activity, Tl(I) and Tl(III) decreased glutathione reductase (GR) expression. However, GR activity was mildly enhanced by Tl(III). Finally, thioredoxin-dependent system was evaluated. Only Tl(I) increased 2-Cys peroxiredoxins (2-Cys Prx) expression, although both cations increased their activity. Tl(I) increased cytosolic thioredoxin reductase (TrxR1) and decreased mitochondrial (TrxR2) expression. Tl(III) had a biphasic effect on TrxR1 expression and slightly increased TrxR2 expression. Despite of this, both cations increased total TrxR activity. Obtained results suggest that in Tl(I)-exposed PC12adh cells, there is an early response to oxidative stress mainly by GSH-dependent system while in Tl(III)-treated cells both GSH- and Trx-dependent systems are involved.
KeywordsThallium Oxidative stress Mitochondria Antioxidant enzymes Antioxidant defense system Glutathione Thioredoxin PC12 cells
Dulbecco’s modified Eagle medium
NG-nitro-l-arginine methyl ester
2,2′-bis(4-Nitrophenyl)-5,5′-diphenyl-3,3′-(3,3′-dimethoxy-4,4′-diphenylene) ditetrazolium chloride
Nitric oxide synthase
Phosphate buffered saline
PC12 cells, adherent variant
Reactive nitrogen species
Reactive oxygen species
Sodium dodecyl sulfate
This work was supported by grants of the University of Buenos Aires (B086 and 20020100100112) and Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT; PICT2013-1018). SVV is a career investigator of the CONICET (National Research Council, Argentina). LCPM was a recipient of an undergraduate fellowship from the University of Buenos Aires (Argentina).
Compliance with ethical standards
Conflict of interest
The authors declare no conflicts of interest.
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