Altered Patterns of Protein Phosphorylation and Synthesis Caused by Methyl Mercury in Cerebellar Granule Cell Culture

Sarafian, Theodore A.; Verity, M. Anthony

doi:10.1111/j.1471-4159.1990.tb04579.x

Cited by 15 publications

(3 citation statements)

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“…Changes in protein phosphorylation patterns by CH 3 Hg + were also described, mainly leading to both in vivo and in vitro elevated phosphorylation (Sarafian and Verity, 1990;Yagame et al, 1994). Tubulin subunits were l l between proteins with excess phosphorylation.…”

Section: Inhibition Of Protein Synthesis and Alteration Of Proteimentioning

confidence: 93%

Neurotoxicity of organomercurial compounds

et al. 2003

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Mercury is a ubiquitous contaminant, and a range of chemical species is generated by human activity and natural environmental change. Elemental mercury and its inorganic and organic compounds have different toxic properties, but all them are considered hazardous in human exposure. In an equimolecular exposure basis, organomercurials with a short aliphatic chain are the most harmful compounds and they may cause irreversible damage to the nervous system. Methylmercury (CH(3)Hg(+)) is the most studied following the neurotoxic outbreaks identified as Minamata disease and the Iraq poisoning. The first description of the CNS pathology dates from 1954. Since then, the clinical neurology, the neuropathology and the mechanisms of neurotoxicity of organomercurials have been widely studied. The high thiol reactivity of CH(3)Hg(+), as well as all mercury compounds, has been suggested to be the basis of their harmful biological effects. However, there is clear selectivity of CH(3)Hg(+) for specific cell types and brain structures, which is not yet fully understood. The main mechanisms involved are inhibition of protein synthesis, microtubule disruption, increase of intracellular Ca(2+) with disturbance of neurotransmitter function, oxidative stress and triggering of excitotoxicity mechanisms. The effects are more damaging during CNS development, leading to alterations of the structure and functionality of the nervous system. The major source of CH(3)Hg(+) exposure is the consumption of fish and, therefore, its intake is practically unavoidable. The present concern is on the study of the effects of low level exposure to CH(3)Hg(+) on human neurodevelopment, with a view to establishing a safe daily intake. Recommendations are 0.4 micro g/kg body weight/day by the WHO and US FDA and, recently, 0.1 micro g/kg body weight/day by the US EPA. Unfortunately, these levels are easily attained with few meals of fish per week, depending on the source of the fish and its position in the food chain.

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Section: Inhibition Of Protein Synthesis and Alteration Of Proteimentioning

confidence: 93%

Neurotoxicity of organomercurial compounds

et al. 2003

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“…This study demonstrates the antioxidant role of the STAT3 signaling pathway for oxidative stress regulation of MeHg-induced toxicity. MeHg has been revealed in numerous studies to modify protein phosphorylation in a concentration-and cell-type-dependent manner, resulting in the dysregulation of signaling pathways (Sarafian and Verity 1990, Yagame, Horigome et al 1994, Ke, Goncalves et al 2019). However, very little is known about the effect of MeHg on the STAT3 signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

JAK2/STAT3 signaling pathway mediates methylmercury toxicity in mouse astrocyte neuronal C8-D1A cell line

Ahmed,

Aschner,

Ferrer

2024

Preprint

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Methylmercury (MeHg) is an environmental pollutant. Consumption of contaminated fish is the main exposure route in humans, leading to severe neurological disorders. Upon ingestion MeHg reaches the brain and selectively accumulates in astrocytes disrupting glutamate and calcium homeostasis and increasing oxidative stress. Despite extensive research, the molecular mechanisms underlying MeHg neurotoxicity remain incompletely understood. The induction of nuclear factor erythroid 2-related factor 2 (Nrf2) and its role activating antioxidant responses during MeHg-induced oxidative injury have garnered significant attention as a potential therapeutic target against MeHg toxicity. However, recent studies indicate that the Nrf2 signaling pathway alone may not be sufficient to mitigate MeHg-induced damage, suggesting the existence of other protective mechanisms. The signal transducer and activator of transcription 3 (STAT3) plays a crucial role in cell growth and survival. Several studies have also highlighted its involvement in regulating redox homeostasis, thereby preventing oxidative stress through mechanisms that involve modulation of nuclear genes that encode electron transport complexes (ETC) and antioxidant enzymes. These characteristics suggest that STAT3 could serve as a viable mechanism to mitigate MeHg toxicity, either in conjunction with or as an alternative to Nrf2 signaling. Our previous findings demonstrated that MeHg activates the STAT3 signaling pathway in the GT1-7 hypothalamic neuronal cell line, suggesting its potential role in promoting neuroprotection. Here, to elucidate the role of the STAT3 signaling pathway in MeHg neurotoxicity, we pharmacologically inhibited STAT3 using AG490 in the C8D1A astrocytic cell line exposed to 10 µM MeHg. Our data demonstrated that pharmacological inhibition of STAT3 phosphorylation exacerbates MeHg-induced mortality, antioxidant responses, and ROS production, suggesting that STAT3 may contribute to neuroprotection against MeHg exposure in astrocytes.

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“…The high-affinity binding of MeHg to selenium groups underlies various observations indicating a protective role for dietary selenium in MeHg toxicity by various mechanisms including sequestration, glutathione (GSH) synthesis, increased GSH peroxidase activity, increased selenoprotein levels, and increased MeHg demethylation (see [115]). Various cellular processes are altered by MeHg exposure in vivo and in vitro, including RNA and protein synthesis [130][131][132][133][134], mitochondrial function (including loss of mitochondrial membrane potential, adenosine triphosphate (ATP) production, and calcium homeostasis, protein phosphorylation) [133,135], and production of reactive oxygen species (ROS) [136][137][138][139]. Various cellular processes are altered by MeHg exposure in vivo and in vitro, including RNA and protein synthesis [130][131][132][133][134], mitochondrial function (including loss of mitochondrial membrane potential, adenosine triphosphate (ATP) production, and calcium homeostasis, protein phosphorylation) [133,135], and production of reactive oxygen species (ROS) [136][137][138][139].…”

Section: Mechanisms Underlying Mehg-mediated Neurotoxicitymentioning

confidence: 99%