Methylmercury can induce Parkinson’s-like neurotoxicity similar to 1-methyl-4- phenylpyridinium: a genomic and proteomic analysis on MN9D dopaminergic neuron cells

Shao, Yueting; Figeys, Daniel; Ning, Zhibin; Mailloux, Ryan J.; Chan, Hing Man

doi:10.2131/jts.40.817

Cited by 28 publications

(16 citation statements)

References 59 publications

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“…and metalloids. Such studies published these past three years in the Journal of Toxicological Sciences investigated the toxicity of many types of metals, including cadmium (Ohtani et al, 2013;Miura et al, 2013;Baba et al, 2014;Du et al, 2014;Park et al, 2015;Lukkhananan et al, 2015), mercury (Yoshida et al, 2013;Kim et al, 2014), methylmercury (Hwang et al, 2013a(Hwang et al, , 2013bIwai-Shimada et al, 2013;Chang et al, 2013;Hirooka et al, 2013;Kim et al, 2013;Watanabe et al, 2013;Shao et al, 2015;Toyama et al, 2015), aluminum (Zhang et al, 2013;Jinzhu et al, 2015), manganese (Fujishiro et al, 2013), uranium (Lestaevel et al, 2013), arsenic (Tokumoto et al, 2013;Wang et al, 2015), arsine (Kato et al, 2014), organic bismuth (Kohri et al, 2015), chromium (Kimura et al, 2015), and tributyltin (Oyanagi et al, 2015). Although methylmercury is one of the organic-inorganic hybrid molecules (the minimum unit!…”

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confidence: 99%

Toxicology of organic-inorganic hybrid molecules: bio-organometallics and its toxicology

2016

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Bio-organometallics is a research strategy of biology that uses organic-inorganic hybrid molecules. The molecules are expected to exhibit useful bioactivities based on the unique structure formed by interaction between the organic structure and intramolecular metal(s). However, studies on both biology and toxicology of organic-inorganic hybrid molecules have been incompletely performed. There can be two types of toxicological studies of bio-organometallics; one is evaluation of organic-inorganic hybrid molecules and the other is analysis of biological systems from the viewpoint of toxicology using organic-inorganic hybrid molecules. Our recent studies indicate that cytotoxicity of hybrid molecules containing a metal that is nontoxic in inorganic forms can be more toxic than that of hybrid molecules containing a metal that is toxic in inorganic forms when the structure of the ligand is the same. Additionally, it was revealed that organic-inorganic hybrid molecules are useful for analysis of biological systems important for understanding the toxicity of chemical compounds including heavy metals.

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confidence: 99%

Toxicology of organic-inorganic hybrid molecules: bio-organometallics and its toxicology

2016

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“…previously been described to impair dopaminergic function and to have similar neurotoxic effects to the well-known nigrostriatal toxicant 1-methyl-4-phenylpyridinium (MPP+, the active metabolite of MPTP) (Dreiem et al, 2009;Shao et al, 2015;Tiernan et al, 2015), we decided to focus on TBBPA and berberine chloride and further analyzed them as well as five other compounds of interest in dose-response experiments.…”

Section: High Content Image Analysis Quantified Cell-type-specific Toxicity In 3d Human Midbrain-like Tissuesmentioning

confidence: 99%

“…PD is the second most common neurodegenerative disease and is marked by loss of dopaminergic neurons in the substantia nigra (Alexander, 2004;Poewe et al, 2017). Approximately 90% of cases are of sporadic and idiopathic origin (Lesage and Brice, 2009;Schulze et al, 2018), and many studies hypothesize that genetic and environmental factors, including exposure to toxicants, may play a role in the long-term etiology of PD (Warner and Schapira, 2003;Sulzer, 2007;Goldman, 2014;Bellou et al, 2016;Tysnes and Storstein, 2017). However, Parkinsonism in humans can also have more direct causes, where specific compounds can selectively and acutely ablate dopaminergic neurons.…”

Section: Introductionmentioning

confidence: 99%

Cell-Type-Specific High Throughput Toxicity Testing in Human Midbrain Organoids

Renner

Becker

Kagermeier

et al. 2021

Front. Mol. Neurosci.

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Toxicity testing is a crucial step in the development and approval of chemical compounds for human contact and consumption. However, existing model systems often fall short in their prediction of human toxicity in vivo because they may not sufficiently recapitulate human physiology. The complexity of three-dimensional (3D) human organ-like cell culture systems (“organoids”) can generate potentially more relevant models of human physiology and disease, including toxicity predictions. However, so far, the inherent biological heterogeneity and cumbersome generation and analysis of organoids has rendered efficient, unbiased, high throughput evaluation of toxic effects in these systems challenging. Recent advances in both standardization and quantitative fluorescent imaging enabled us to dissect the toxicities of compound exposure to separate cellular subpopulations within human organoids at the single-cell level in a framework that is compatible with high throughput approaches. Screening a library of 84 compounds in standardized human automated midbrain organoids (AMOs) generated from two independent cell lines correctly recognized known nigrostriatal toxicants. This approach further identified the flame retardant 3,3′,5,5′-tetrabromobisphenol A (TBBPA) as a selective toxicant for dopaminergic neurons in the context of human midbrain-like tissues for the first time. Results were verified with high reproducibility in more detailed dose-response experiments. Further, we demonstrate higher sensitivity in 3D AMOs than in 2D cultures to the known neurotoxic effects of the pesticide lindane. Overall, the automated nature of our workflow is freely scalable and demonstrates the feasibility of quantitatively assessing cell-type-specific toxicity in human organoids in vitro.

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“…MeHg impairs the central nervous system, suggesting that MeHg is relevant to the onset of neurodegenerative diseases, such as AD, PD, and ALS [121,122,123,124]. Additionally, it has been reported that MeHg affects fetal neurodevelopment via prenatal exposure to MeHg [125].…”

Section: Mehg and Er Stressmentioning

confidence: 99%

The Emerging Role of Electrophiles as a Key Regulator for Endoplasmic Reticulum (ER) Stress

Takasugi

Hiraoka

Nakahara

et al. 2019

IJMS

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The unfolded protein response (UPR) is activated by the accumulation of misfolded proteins in the endoplasmic reticulum (ER), which is called ER stress. ER stress sensors PERK, IRE1, and ATF6 play a central role in the initiation and regulation of the UPR; they inhibit novel protein synthesis and upregulate ER chaperones, such as protein disulfide isomerase, to remove unfolded proteins. However, when recovery from ER stress is difficult, the UPR pathway is activated to eliminate unhealthy cells. This signaling transition is the key event of many human diseases. However, the precise mechanisms are largely unknown. Intriguingly, reactive electrophilic species (RES), which exist in the environment or are produced through cellular metabolism, have been identified as a key player of this transition. In this review, we focused on the function of representative RES: nitric oxide (NO) as a gaseous RES, 4-hydroxynonenal (HNE) as a lipid RES, and methylmercury (MeHg) as an environmental organic compound RES, to outline the relationship between ER stress and RES. Modulation by RES might be a target for the development of next-generation therapy for ER stress-associated diseases.

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Methylmercury can induce Parkinson’s-like neurotoxicity similar to 1-methyl-4- phenylpyridinium: a genomic and proteomic analysis on MN9D dopaminergic neuron cells

Cited by 28 publications

References 59 publications

Toxicology of organic-inorganic hybrid molecules: bio-organometallics and its toxicology

Toxicology of organic-inorganic hybrid molecules: bio-organometallics and its toxicology

Cell-Type-Specific High Throughput Toxicity Testing in Human Midbrain Organoids

The Emerging Role of Electrophiles as a Key Regulator for Endoplasmic Reticulum (ER) Stress

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