title: Glutamate‑mediated effects of caffeine and interferon‑γ on mercury-induced toxicity.
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.
authors.affiliation: Department of Toxicology, Faculty of Pharmacy, Gazi University, Ankara 06330, Turkey.
authors.forename: Ayse Basak
authors.initials: AB
authors.lastname: Engin
authors.affiliation: Institute of Biotechnology, Ankara University, Ankara 06110, Turkey.
authors.forename: Evren Doruk
authors.initials: ED
authors.lastname: Engin
authors.affiliation: Scientific Educational Center of Nanotechnology, Far Eastern Federal University, Engineering School, Vladivostok 690950, Russia.
authors.forename: Kirill
authors.initials: K
authors.lastname: Golokhvast
authors.affiliation: Laboratory of Clinical Virology, Medical School, University of Crete, Heraklion 71003, Greece.
authors.forename: Demetrios A
authors.initials: DA
authors.lastname: Spandidos
authors.affiliation: Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, Heraklion 71003, Greece.
authors.forename: Aristides M
authors.initials: AM
authors.lastname: Tsatsakis
mesh_terms: D002110:Caffeine / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018698:Glutamic Acid / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008628:Mercury / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D002110:Caffeine; D018698:Glutamic Acid; D007371:Interferon-gamma; D008628:Mercury