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


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ENGİN A. B. , ENGİN E. D. , Golokhvast K., Spandidos D. A. , Tsatsakis A. M.

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, vol.39, no.5, pp.1215-1223, 2017 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 39 Issue: 5
  • Publication Date: 2017
  • Doi Number: 10.3892/ijmm.2017.2937
  • Journal Name: INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.1215-1223
  • Keywords: methyl mercury, mercury chloride, caffeine, interferon-gamma, neurotoxicity, glutamine, TRANSENDOTHELIAL MIGRATION, ADENOSINE RECEPTORS, OXIDATIVE STRESS, METHYLMERCURY, GLUTATHIONE, NEURONS, BRAIN, CELLS, NEUROTOXICITY, TRANSPORT
  • Gazi University Affiliated: Yes

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-gamma (IFN-gamma). The SH-SY5Y cells were exposed to 1, 2 and 5 mu M 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 mu M caffeine. The total mitochondrial metabolic activity and oxidative stress intensity coefficient were determined in the 1 ng/ml IFN-gamma-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 glutaminecontaining medium. IFN-gamma 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-gamma, caffeine decreased the MeHg-induced average oxidative stress only by half. Thereby, our data indicate that the IFN-gamma stimulation of mercury-exposed dopaminergic neurons in neuroinflammatory diseases may diminish the neuroprotective effects of caffeine.