Open Access

Glutamate‑mediated effects of caffeine and interferon‑γ on mercury-induced toxicity

  • Authors:
    • Ayse Basak Engin
    • Evren Doruk Engin
    • Kirill Golokhvast
    • Demetrios A. Spandidos
    • Aristides M. Tsatsakis
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  • Published online on: March 27, 2017     https://doi.org/10.3892/ijmm.2017.2937
  • Pages: 1215-1223
  • Copyright: © Engin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The molecular mechanisms mediating mercury‑induced neurotoxicity are not yet completely understood. Thus, the aim of this study was to investigate whether the severity of MeHg‑ and HgCl2‑mediated cytotoxicity to SH‑SY5Y human dopaminergic neurons can be attenuated by regulating glutamate‑mediated signal‑transmission through caffeine and interferon‑γ (IFN‑γ). The SH‑SY5Y cells were exposed to 1, 2 and 5 µM of either MeHgCl2 or HgCl2 in the presence or absence of L‑glutamine. To examine the effect of adenosine receptor antagonist, the cells were treated with 10 and 20 µM caffeine. The total mitochondrial metabolic activity and oxidative stress intensity coefficient were determined in the 1 ng/ml IFN‑γ‑ and glutamate‑stimulated SH‑SY5Y cells. Following exposure to mercury, the concentration‑dependent decrease in mitochondrial metabolic activity inversely correlated with oxidative stress intensity. MeHg was more toxic than HgCl2. Mercury‑induced neuronal death was dependent on glutamate‑mediated excitotoxicity. Caffeine reduced the mercury‑induced oxidative stress in glutamine-containing medium. IFN‑γ treatment decreased cell viability and increased oxidative stress in glutamine‑free medium, despite caffeine supplementation. Although caffeine exerted a protective effect against MeHg-induced toxicity with glutamate transmission, under co‑stimulation with glutamine and IFN‑γ, caffeine decreased the MeHg‑induced average oxidative stress only by half. Thereby, our data indicate that the IFN‑γ stimulation of mercury‑exposed dopaminergic neurons in neuroinflammatory diseases may diminish the neuroprotective effects of caffeine.
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May-2017
Volume 39 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Engin AB, Engin ED, Golokhvast K, Spandidos DA and Tsatsakis AM: Glutamate‑mediated effects of caffeine and interferon‑γ on mercury-induced toxicity. Int J Mol Med 39: 1215-1223, 2017.
APA
Engin, A.B., Engin, E.D., Golokhvast, K., Spandidos, D.A., & Tsatsakis, A.M. (2017). Glutamate‑mediated effects of caffeine and interferon‑γ on mercury-induced toxicity. International Journal of Molecular Medicine, 39, 1215-1223. https://doi.org/10.3892/ijmm.2017.2937
MLA
Engin, A. B., Engin, E. D., Golokhvast, K., Spandidos, D. A., Tsatsakis, A. M."Glutamate‑mediated effects of caffeine and interferon‑γ on mercury-induced toxicity". International Journal of Molecular Medicine 39.5 (2017): 1215-1223.
Chicago
Engin, A. B., Engin, E. D., Golokhvast, K., Spandidos, D. A., Tsatsakis, A. M."Glutamate‑mediated effects of caffeine and interferon‑γ on mercury-induced toxicity". International Journal of Molecular Medicine 39, no. 5 (2017): 1215-1223. https://doi.org/10.3892/ijmm.2017.2937