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

Engin, Ayşe Başak; Engin, Evren Doruk; Golokhvast, Kirill S.; Spandidos, Demetrios Α.; Tsatsakis, Aristidis

doi:10.3892/ijmm.2017.2937

Cited by 16 publications

(6 citation statements)

References 57 publications

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“…The objective of the present study was to investigate in vitro cytotoxic and immune functional effects of Hg 2+ exposure on two chicken immune cell lines (HD‐11 macrophage and DT40 B‐lymphocytes as models for specific avian immune cell types), after a viral‐like challenge. Similar EC50 values for cell viability (~30 µM) were found for both cell lines after Hg 2+ exposure for 24 h (Figure 1 and Table 1 ), which were in the same range of the EC50 values for Hg 2+ from other in vitro studies using mammalian immune cells (Yamamoto et al, 1998 ; De Guise et al, 2000 ; Wataha et al, 2000 ; Kim & Sharma, 2004 ; Engin et al, 2017 ; David et al, 2020 ). The poly I:C induced cell metabolic activity only in HD‐11 macrophage cells but not in DT40 B‐cells (Figure 1 ), but after 48 h of exposure, only DT40 cells showed an increased metabolic activity after poly I:C challenge (Figure 6B and D).…”

Section: Discussionsupporting

confidence: 82%

Modulatory Effects of Mercury (II) Chloride (HgCl₂) on Chicken Macrophage and B‐Lymphocyte Cell Lines with Viral‐Like Challenges In Vitro

Han

García-Mendoza

Berg

et al. 2021

Enviro Toxic and Chemistry

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Mercury (Hg) is a toxic trace metal ubiquitously distributed in the environment. Inorganic mercury (as HgCl 2 ) can cause immunotoxicity in birds, but the mechanisms of action are still not fully resolved, especially with respect to responses to viral infections. To investigate the potential immunomodulatory effects of Hg 2+ on specific cell types of the avian immune system, chicken macrophage (HD-11) and B-lymphocyte (DT40) cell lines were applied as in vitro models for the innate and adaptive immune systems, respectively. The cells were stimulated with synthetic double-stranded RNA, which can be recognized by toll-like receptor-3 to mimic a viral infection. The Hg 2+ showed concentration-dependent cytotoxicity in both cell lines, with similar median effect concentrations at 30 µM. The cytotoxicity of Hg 2+ was closely related to glutathione (GSH) depletion and reactive oxygen species induction, whereas the de novo synthesis of GSH acted as a primary protective strategy. Nitric oxide produced by activated macrophages was strongly inhibited by Hg 2+ , and was also influenced by cellular GSH levels. Cell proliferation, gene expression of microRNA-155, and cellular IgM levels in B cells were decreased at noncytotoxic Hg 2+ concentrations. The secretion of antiviral interferon-α was induced by Hg 2+ in both cell lines. Overall, our results suggest that Hg 2+ exposure can cause immunomodulatory effects in birds by disrupting immune cell proliferation and cytokine production, and might result in disorders of the avian immune system.

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Section: Discussionsupporting

confidence: 82%

Modulatory Effects of Mercury (II) Chloride (HgCl₂) on Chicken Macrophage and B‐Lymphocyte Cell Lines with Viral‐Like Challenges In Vitro

Han

García-Mendoza

Berg

et al. 2021

Enviro Toxic and Chemistry

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“…Use viral proteins to maintain survival and HIV associated inflammation 55,56 ; 5. Activate a “cancer-like program” to survive independently of efficient blood circulation 57,58 ; 6. Activate novel forms of viral reactivation 8,24,59,60 ; 7.…”

Section: Discussionmentioning

confidence: 99%

HIV infection and latency induce a unique metabolic signature in human macrophages

Castellano¹,

Prevedel²,

Valdebenito

et al. 2019

Sci Rep

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Currently, a major barrier to curing HIV infection is the generation of tissue-associated, non-replicating, long-lasting viral reservoirs that are refractory to therapy and can be reactivated upon anti-retroviral therapy interruption. One of these reservoirs are latently HIV-infected macrophages. Here, we show that HIV infection of macrophages results in survival of a small population of infected cells that are metabolically altered and characterized by mitochondrial fusion, lipid accumulation, and reduced mitochondrial ATP production. No changes in glycolysis were detected. Metabolic analysis indicated an essential role of succinate and other TCA metabolites in the tricarboxylic acid (TCA) cycle in mediating lipid accumulation and oxidative phosphorylation (OXPHOS) in the mitochondria. Furthermore, we show that while uninfected and HIV infected macrophages use fatty acids and glucose as primary sources of energy, surviving HIV infected macrophages also use glutamine/glutamate as a major energy source, and blocking these new sources of energy resulted in the killing of latent HIV infected macrophages. Together, our data provide a new understanding of the formation, properties, and potential novel ways to eliminate macrophage viral reservoirs.

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“…Glutathione is known as a neuronal antioxidant essential for the removal of ROS and the reduction of oxidative stress. Excessive glutamate indicates the depletion of glutathione, which is caused by inhibiting cysteine uptake (38). In this study, glutamate treatment significantly decrease dthe glutathione contents.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective effects of Scrophularia buergeriana extract against glutamate-induced toxicity in SH-SY5Y cells

et al. 2019

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The aim of this study was to investigate the antioxidant and anti-apoptotic activities, as well as the underlying mechanisms of action, of Scrophularia buergeriana ( S. buergeriana ) extract (SBE) in glutamate-induced SH-SY5Y cell death. The roots of S. buergeriana were extracted with 70% ethanol, and standardized SBE was used in this study. To induce cytotoxicity, the SH-SY5Y cells were exposed to glutamate for 3 h, or pre-treated with SBE for 1 h, and subsequently incubated with glutamate for 3 h. The neuro-protective effects were assessed by measuring cell viability and the total glutathione contents using commercial kits. The antioxidant and anti-apoptotic mechanisms of action of SBE were evaluated by western blot analysis. The results confirmed that glutamate-induced toxicity was caused by reactive oxygen species (ROS) production, leading to oxidative stress and DNA damage, thus leading to cell death. However, treatment of the SH-SY5Y cells with SBE significantly increased the viability of the cells exposed to glutamate by upregulating the levels of antioxidant proteins, such as superoxide dismutase (SOD)1, SOD2 and glutathione peroxidase-1 (GPx-1), and directly enhancing the total glutathione contents. Furthermore, SBE attenuated DNA impairment and decreased B-cell lymphoma-2 (Bcl-2)-associated X protein (Bax), cleaved caspase-3 and cleaved poly(adenosine diphosphate (ADP)-ribose) polymerase (PARP) activation. In addition, SBE upregulated Bcl-2 expression via p38 mitogen-activated protein kinases (MAPKs). On the whole, the findings of this study demonstrated that SBE exerts neuroprotective effects against glutamate-induced cell toxicity through its antioxidant and anti-apoptotic activities.

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

Cited by 16 publications

References 57 publications

Modulatory Effects of Mercury (II) Chloride (HgCl₂) on Chicken Macrophage and B‐Lymphocyte Cell Lines with Viral‐Like Challenges In Vitro

Modulatory Effects of Mercury (II) Chloride (HgCl₂) on Chicken Macrophage and B‐Lymphocyte Cell Lines with Viral‐Like Challenges In Vitro

HIV infection and latency induce a unique metabolic signature in human macrophages

Neuroprotective effects of Scrophularia buergeriana extract against glutamate-induced toxicity in SH-SY5Y cells

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

Cited by 16 publications

References 57 publications

Modulatory Effects of Mercury (II) Chloride (HgCl2) on Chicken Macrophage and B‐Lymphocyte Cell Lines with Viral‐Like Challenges In Vitro

Modulatory Effects of Mercury (II) Chloride (HgCl2) on Chicken Macrophage and B‐Lymphocyte Cell Lines with Viral‐Like Challenges In Vitro

HIV infection and latency induce a unique metabolic signature in human macrophages

Neuroprotective effects of Scrophularia buergeriana extract against glutamate-induced toxicity in SH-SY5Y cells

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Product

Resources

About

Modulatory Effects of Mercury (II) Chloride (HgCl₂) on Chicken Macrophage and B‐Lymphocyte Cell Lines with Viral‐Like Challenges In Vitro

Modulatory Effects of Mercury (II) Chloride (HgCl₂) on Chicken Macrophage and B‐Lymphocyte Cell Lines with Viral‐Like Challenges In Vitro