Arsenic Exposure and Compromised Protein Quality Control

Tam, Lok Ming; Wang, Yinsheng

doi:10.1021/acs.chemrestox.0c00107

Cited by 31 publications

(23 citation statements)

References 120 publications

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“…Here, down-regulation of EIF5A As/Ctrl may contribute to the NaAsO 2 -induced L-02 cell apoptosis. Arsenic can also cause protein misfolding and induce an increase in HSP protein expression (Tam and Wang, 2020). In this study, the expression of heat shock protein HSPE1 increased in As/Ctrl group.…”

Section: Discussionsupporting

confidence: 45%

Protective Effect of Dictyophora Polysaccharides on Sodium Arsenite-Induced Hepatotoxicity: A Proteomics Study

Shen

Huang

et al. 2021

Front. Pharmacol.

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The purpose of this study is to understand the mechanism of sodium arsenite (NaAsO2)-induced apoptosis of L-02 human hepatic cells, and how Dictyophora polysaccharide (DIP) protects L-02 cells from arsenic-induced apoptosis. The results revealed that DIP pretreatment inhibited NaAsO2 induced L-02 cells apoptosis by increasing anti-apoptotic Bcl-2 expression and decreasing pro-apoptotic Bax expression. Proteomic analysis showed that arsenic treatment disrupted the expression of metabolism and apoptosis associated proteins, including ribosomal proteins (RPs). After pretreatment with DIP, the expression levels of these proteins were reversed or restored. For the first time, it was observed that the significant decrease of cytoplasmic RPs and the increase of mitochondrial RPs were related to human normal cell apoptosis induced by arsenic. This is also the first report that the protective effect of DIP on cells was related to RPs. The results highlight the relationship between RPs and apoptosis, as well as the relationship between RPs and DIP attenuating arsenic-induced apoptosis.

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Section: Discussionsupporting

confidence: 45%

Protective Effect of Dictyophora Polysaccharides on Sodium Arsenite-Induced Hepatotoxicity: A Proteomics Study

Shen

Huang

et al. 2021

Front. Pharmacol.

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“…, ubiquitin-proteasome system and ER stress-induced autophagy. This cross-talk could mean that chronic As 3+ exposure brings about proteome-wide changes not only by modulating the epigenome and the transcriptome, but also the cellular degradome, as recent studies suggest (Dodson et al 2018 ; Tam and Wang 2020 ).…”

Section: Discussionmentioning

confidence: 95%

Dynamic alteration in miRNA and mRNA expression profiles at different stages of chronic arsenic exposure-induced carcinogenesis in a human cell culture model of skin cancer

et al. 2021

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Chronic arsenic exposure causes skin cancer, although the underlying molecular mechanisms are not well defined. Altered microRNA and mRNA expression likely play a pivotal role in carcinogenesis. Changes in genome-wide differential expression of miRNA and mRNA at 3 strategic time points upon chronic sodium arsenite (As3+) exposure were investigated in a well-validated HaCaT cell line model of arsenic-induced cutaneous squamous cell carcinoma (cSCC). Quadruplicate independent HaCaT cell cultures were exposed to 0 or 100 nM As3+ for up to 28-weeks (wk). Cell growth was monitored throughout the course of exposure and epithelial-mesenchymal transition (EMT) was examined employing immunoblot. Differentially expressed miRNA and mRNA profiles were generated at 7, 19, and 28-wk by RNA-seq, followed by identification of differentially expressed mRNA targets of differentially expressed miRNAs through expression pairing at each time point. Pathway analyses were performed for total differentially expressed mRNAs and for the miRNA targeted mRNAs at each time point. RNA-seq predictions were validated by immunoblot of selected target proteins. While the As3+-exposed cells grew slower initially, growth was equal to that of unexposed cells by 19-wk (transformation initiation), and exposed cells subsequently grew faster than passage-matched unexposed cells. As3+-exposed cells had undergone EMT at 28-wk. Pathway analyses demonstrate dysregulation of carcinogenesis-related pathways and networks in a complex coordinated manner at each time point. Immunoblot data largely corroborate RNA-seq predictions in the endoplasmic reticulum stress (ER stress) pathway. This study provides a detailed molecular picture of changes occurring during the arsenic-induced transformation of human keratinocytes.

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“…Compelling evidence from recent studies suggests that chronic exposure to inorganic arsenic can disrupt protein quality control and clearance systems, which contribute to the pathobiology of proteinopathic brain disorders such as AD. Arsenic-mediated post-translational modifications of proteins and disruptions of ubiquitination may culminate in impairment in proteostasis [ 60 ]. Genome-wide imaging screen analysis uncovers the molecular causes of arsenite-mediated protein aggregation and toxicity studied on Saccharomyces cerevisiae deletion mutants [ 61 ].…”

Section: Molecular Basis Of Arsenic Toxicity and Its Implication In Ad Pathobiologymentioning

confidence: 99%

Exposure to Environmental Arsenic and Emerging Risk of Alzheimer’s Disease: Perspective Mechanisms, Management Strategy, and Future Directions

Rahman

Hannan

Uddin

et al. 2021

Toxics

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Alzheimer’s disease (AD) is one of the most prevailing neurodegenerative diseases, characterized by memory dysfunction and the presence of hyperphosphorylated tau and amyloid β (Aβ) aggregates in multiple brain regions, including the hippocampus and cortex. The exact etiology of AD has not yet been confirmed. However, epidemiological reports suggest that populations who were exposed to environmental hazards are more likely to develop AD than those who were not. Arsenic (As) is a naturally occurring environmental risk factor abundant in the Earth’s crust, and human exposure to As predominantly occurs through drinking water. Convincing evidence suggests that As causes neurotoxicity and impairs memory and cognition, although the hypothesis and molecular mechanism of As-associated pathobiology in AD are not yet clear. However, exposure to As and its metabolites leads to various pathogenic events such as oxidative stress, inflammation, mitochondrial dysfunctions, ER stress, apoptosis, impaired protein homeostasis, and abnormal calcium signaling. Evidence has indicated that As exposure induces alterations that coincide with most of the biochemical, pathological, and clinical developments of AD. Here, we overview existing literature to gain insights into the plausible mechanisms that underlie As-induced neurotoxicity and the subsequent neurological deficits in AD. Prospective strategies for the prevention and management of arsenic exposure and neurotoxicity have also been discussed.

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Arsenic Exposure and Compromised Protein Quality Control

Cited by 31 publications

References 120 publications

Protective Effect of Dictyophora Polysaccharides on Sodium Arsenite-Induced Hepatotoxicity: A Proteomics Study

Protective Effect of Dictyophora Polysaccharides on Sodium Arsenite-Induced Hepatotoxicity: A Proteomics Study

Dynamic alteration in miRNA and mRNA expression profiles at different stages of chronic arsenic exposure-induced carcinogenesis in a human cell culture model of skin cancer

Exposure to Environmental Arsenic and Emerging Risk of Alzheimer’s Disease: Perspective Mechanisms, Management Strategy, and Future Directions

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