Origins, fate, and actions of methylated trivalent metabolites of inorganic arsenic: progress and prospects

Stýblo, Miroslav; Venkatratnam, Abhishek; Fry, Rebecca C.; Thomas, David J.

doi:10.1007/s00204-021-03028-w

Cited by 43 publications

(30 citation statements)

References 211 publications

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“…To date, a number of soil microbes have been demonstrated to produce MAs(III), either by MAs(V) reduction (Yoshinaga et al, 2011) or by methylation of As(III) (Qin et al, 2006). MAs(III) is highly toxic and has been shown to have antibiotic activity (Li et al, 2016;Styblo et al, 2021). Further methylation of MAs(III) to di-and trimethyl trivalent species may be protective if those species are rapidly oxidized or volatilized.…”

Section: Discussionmentioning

confidence: 99%

“…The toxicity of arsenic highly depends on its species. Methylarsenite (MAs(III)), an intermediate product of arsenic biomethylation, is more toxic and potentially carcinogenic than either the corresponding pentavalent species or inorganic arsenite (As(III)), and may account for the majority of arsenic-related diseases (Yoshinaga-Sakurai et al, 2020;Li et al, 2021;Styblo et al, 2021). MAs(III) is stable in the anoxic environment that existed before the Great Oxidation Event (GOE) (Chen et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

“…Thus methylation is an arsenic detoxification pathway for aerobes that harbour arsM genes. However, under anoxic conditions, As(III)-methylating anaerobes produce highly toxic MAs(III), which is actively extruded into their surroundings, posing an environmental challenge for their neighbours without MAs(III) resistant genes (Li et al, 2016;Styblo et al, 2021). Thus, As(III) methylation is considered an antibiotic-producing pathway in anaerobes.…”

Section: Introductionmentioning

confidence: 99%

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Functional characterization of the methylarsenite‐inducible arsRM operon from Noviherbaspirillum denitrificans HC18

Zhang

Chen

et al. 2022

Environmental Microbiology

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Microbial arsenic methylation by arsenite (As(III)) Sadenosylmethionine methyltransferases (ArsMs) can produce the intermediate methylarsenite (MAs(III)), which is highly toxic and is used by some microbes as an antibiotic. Other microbes have evolved mechanisms to detoxify MAs(III). In this study, an arsRM operon was identified in the genome of an MAs(III)methylation strain Noviherbaspirillum denitrificans HC18. The arsM gene (NdarsM) is located downstream of an open reading frame encoding an MAs(III)responsive transcriptional regulator (NdArsR). The N. denitrificans arsRM genes are co-transcribed whose expression is significantly induced by MAs(III), likely by alleviating the repressive effect of ArsR on arsRM transcription. Both in vivo and in vitro assays showed that NdArsM methylates MAs(III) to dimethyl-and trimethyl-arsenicals but does not methylate As(III). Heterologous expression of NdarsM in arsenicsensitive Escherichia coli AW3110 conferred resistance to MAs(III) but not As(III). NdArsM has the four conserved cysteine residues present in most ArsMs, but only two of them are essential for MAs(III) methylation. The ability to methylate MAs(III) by enzymes such as NdArsM may be an evolutionary step originated from enzymes capable of methylating As(III). This finding reveals a mechanism employed by microbes such as N. denitrificans HC18 to detoxify MAs(III) by further methylation. AbbreviationsDMAs(V) dimethylarsenate HPLC high-performance liquid chromatography MAs(III) methylarsenite MAs(V) methylarsenate TMAs(V)O trimethylarsine oxide

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Functional characterization of the methylarsenite‐inducible arsRM operon from Noviherbaspirillum denitrificans HC18

Zhang

Chen

et al. 2022

Environmental Microbiology

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“…The capacity of arsenic methylation is a well-known modifier of arsenic-induced skin lesions, diabetes, and metabolic syndromes [ 28 , 29 , 30 , 31 ]. Inorganic arsenic (iAs) ingested from water and foods is metabolized to methylated arsenic species by arsenic (+3 oxidation state) methyltransferase (AS3MT), mainly in the liver in humans [ 32 , 33 ]. AS3MT methylates iAs to monomethylarsonic acid (MMA) in the first step and then to dimethylarsinic acid (DMA) in the second step.…”

Section: Introductionmentioning

confidence: 99%

“…Methylation of iAs to organic metabolites mainly functions as detoxification and elimination pathways of arsenic. However, arsenic methylation also produces highly toxic and unstable intermediates, as well as methylated trivalent forms of arsenic such as MMAs III and DMAs III [ 33 , 34 , 35 ]. Thus, arsenic methylation has dichotomous roles in the detoxification and metabolic activation of arsenic.…”

Section: Introductionmentioning

confidence: 99%

Arsenic Secondary Methylation Capacity Is Inversely Associated with Arsenic Exposure-Related Muscle Mass Reduction

Sarker

Tony

Siddique

et al. 2021

IJERPH

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Skeletal muscle mass reduction has been implicated in insulin resistance (IR) that promotes cardiometabolic diseases. We have previously reported that arsenic exposure increases IR concomitantly with the reduction of skeletal muscle mass among individuals exposed to arsenic. The arsenic methylation capacity is linked to the susceptibility to some arsenic exposure-related diseases. However, it remains unknown whether the arsenic methylation capacity affects the arsenic-induced reduction of muscle mass and elevation of IR. Therefore, this study examined the associations between the arsenic methylation status and skeletal muscle mass measures with regard to IR by recruiting 437 participants from low- and high-arsenic exposure areas in Bangladesh. The subjects’ skeletal muscle mass was estimated by their lean body mass (LBM) and serum creatinine levels. Subjects’ drinking water arsenic concentrations were positively associated with total urinary arsenic concentrations and the percentages of MMA, as well as inversely associated with the percentages of DMA and the secondary methylation index (SMI). Subjects’ LBM and serum creatinine levels were positively associated with the percentage of DMA and SMI, as well as inversely associated with the percentage of MMA. HOMA-IR showed an inverse association with SMI, with a confounding effect of sex. Our results suggest that reduced secondary methylation capacity is involved in the arsenic-induced skeletal muscle loss that may be implicated in arsenic-induced IR and cardiometabolic diseases.

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Melatonin ameliorates arsenic‐induced cardiotoxicity through the regulation of the Sirt1/Nrf2 pathway in rats

et al. 2023

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Chronic arsenic (As) exposure, mainly as a result of drinking contaminated water, is associated with cardiovascular diseases. Mitochondrial dysfunction, oxidative stress, inflammation, apoptosis, and autophagy have been suggested as the molecular etiology of As cardiotoxicity. Melatonin (Mel) is a powerful antioxidant. Mel improves diabetic cardiomyopathy, cardiac remodeling, and heart failure. Following pre-treatment with Mel (10, 20, or 30 mg/kg/day i.p.), rats were orally gavaged with As (15 mg/kg/day) for 28 days. Electrocardiographic findings showed that Mel decreased the As-mediated QT interval prolongation. The effects of As on cardiac levels of glutathione (GSH) and malondialdehyde (MDA) were reversed by Mel pretreatment. Mel also modulated the Sirt1 and Nrf2 expressions promoted by As. Mel down-regulated autophagy markers such as Beclin-1 expression and the LC3-II/I ratio. Moreover, the cardiac expression of cleaved-caspase-3 and Bax/Bcl-2 ratio was decreased by Mel pretreatment. Reduced expression of miR-34a and miR-144 by As were reversed by Mel. The histopathological changes of cardiac injury

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Origins, fate, and actions of methylated trivalent metabolites of inorganic arsenic: progress and prospects

Cited by 43 publications

References 211 publications

Functional characterization of the methylarsenite‐inducible arsRM operon from Noviherbaspirillum denitrificans HC18

Functional characterization of the methylarsenite‐inducible arsRM operon from Noviherbaspirillum denitrificans HC18

Arsenic Secondary Methylation Capacity Is Inversely Associated with Arsenic Exposure-Related Muscle Mass Reduction

Melatonin ameliorates arsenic‐induced cardiotoxicity through the regulation of the Sirt1/Nrf2 pathway in rats

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