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Superoxide anion radical (O2(-)) degrades methylmercury to inorganic mercury in human astrocytoma cell line (CCF-STTG1).
- Source :
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Chemico-biological interactions [Chem Biol Interact] 2015 Sep 05; Vol. 239, pp. 46-55. Date of Electronic Publication: 2015 Jun 22. - Publication Year :
- 2015
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Abstract
- Methylmercury (MeHg) is a global pollutant that is affecting the health of millions of people worldwide. However, the mechanism of MeHg toxicity still remains somewhat elusive and there is no treatment. It has been known for some time that MeHg can be progressively converted to inorganic mercury (iHg) in various tissues including the brain. Recent work has suggested that cleavage of the carbon-metal bond in MeHg in a biological environment is facilitated by reactive oxygen species (ROS). However, the oxyradical species that actually mediates this process has not been identified. Here, we provide evidence that superoxide anion radical (O2(-)) can convert MeHg to iHg. The calculated second-order rate constant for the degradation of 1μM MeHg by O2(-) generated by xanthine/xanthine oxidase was calculated to be 2×10(5)M(-1)s(-1). We were also able to show that this bioconversion can proceed in intact CCF-STTG1 human astrocytoma cells exposed to paraquat (PQ), a O2(-) generating viologen. Notably, exposure of cells to increasing amounts of PQ led to a dose dependent increase in both MeHg and iHg. Indeed, a 24h exposure to 500μM PQ induced a ∼13-fold and ∼18-fold increase in intracellular MeHg and iHg respectively. These effects were inhibited by superoxide dismutase mimetic MnTBAP. In addition, we also observed that a 24h exposure to a biologically relevant concentration of MeHg (1μM) did not induce cell death, oxidative stress, or even changes in cellular O2(-) and H2O2. However, co-exposure to PQ enhanced MeHg toxicity which was associated with a robust increase in cell death and oxidative stress. Collectively our results show that O2(-) can bioconvert MeHg to iHg in vitro and in intact cells exposed to conditions that simulate high intracellular O2(-) production. In addition, we show for the first time that O2(-) mediated degradation of MeHg to iHg enhances the toxicity of MeHg by facilitating an accumulation of both MeHg and iHg in the intracellular environment.<br /> (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)
- Subjects :
- Astrocytoma drug therapy
Astrocytoma pathology
Cell Death drug effects
Cell Line, Tumor drug effects
Central Nervous System Neoplasms drug therapy
Central Nervous System Neoplasms pathology
Humans
Hydrogen Peroxide metabolism
Methylmercury Compounds administration & dosage
Methylmercury Compounds metabolism
Methylmercury Compounds toxicity
Oxidative Stress drug effects
Paraquat pharmacology
Reactive Oxygen Species metabolism
Superoxide Dismutase metabolism
Xanthine metabolism
Xanthine Oxidase metabolism
Astrocytoma metabolism
Central Nervous System Neoplasms metabolism
Mercury metabolism
Methylmercury Compounds pharmacokinetics
Superoxides metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7786
- Volume :
- 239
- Database :
- MEDLINE
- Journal :
- Chemico-biological interactions
- Publication Type :
- Academic Journal
- Accession number :
- 26111762
- Full Text :
- https://doi.org/10.1016/j.cbi.2015.06.028