Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Buenos Aires, Argentina.
Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Facultad de Farmacia y Bioquímica, Buenos Aires, Argentina.
Arch Toxicol. 2018 Jan;92(1):195-211. doi: 10.1007/s00204-017-2056-0. Epub 2017 Sep 2.
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 HO generation while Tl(III) induced HO 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.
铊（Tl）是一种有毒重金属，无论是在体外还是体内都会引起氧化应激。在这项工作中，我们评估了暴露于 Tl（I）或 Tl（III）（10-100 μM）0.5-6 h 的贴壁 PC12（PC12adh）细胞中活性氧（ROS）和活性氮（RNS）反应性物质的产生。在这个系统中，Tl（I）主要诱导 HO 的产生，而 Tl（III）诱导 HO 和 ONOO 的产生。两种阳离子均增强了 iNOS 的表达和活性，降低了 CuZnSOD 的表达，但不影响其活性。Tl（I）增加了 MnSOD 的表达和活性，但 Tl（III）降低了它们。NADPH 氧化酶（NOX）活性在整个评估期间保持不变。在孵育 6 小时后，氧化剂水平恢复到基线值，表明抗氧化防御系统对阳离子引起的氧化损伤做出了反应。Tl 还影响了谷胱甘肽依赖的系统：虽然 Tl（III）增加了谷胱甘肽过氧化物酶（GPx）的表达和活性，但 Tl（I）和 Tl（III）降低了谷胱甘肽还原酶（GR）的表达。然而，Tl（III）轻度增强了 GR 的活性。最后，评估了硫氧还蛋白依赖的系统。只有 Tl（I）增加了 2-Cys 过氧化物酶（2-Cys Prx）的表达，尽管两种阳离子都增加了它们的活性。Tl（I）增加了细胞质硫氧还蛋白还原酶（TrxR1）的表达并降低了线粒体（TrxR2）的表达。Tl（III）对 TrxR1 的表达有双相作用，略微增加了 TrxR2 的表达。尽管如此，两种阳离子均增加了总 TrxR 活性。研究结果表明，在 Tl（I）暴露的 PC12adh 细胞中，存在一种主要由 GSH 依赖系统引起的早期氧化应激反应，而在 Tl（III）处理的细胞中，GSH 和 Trx 依赖系统均参与其中。
