Role of Arsenic (+3 Oxidation State) Methyltransferase in Arsenic Metabolism and Toxicity

Sumi, Daigo; Himeno, Seiichiro

doi:10.1248/bpb.b212015

Cited by 34 publications

(18 citation statements)

References 47 publications

(50 reference statements)

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“…6B). Arsenic (+3 oxidation state) methyltransferase (As3mt) is the arsenic methyltransferase that protects against arsenic toxicity by converting inorganic arsenic to the methylated metabolite (Sumi and Himeno, 2012). Hepatic As3mt mRNAs were moderately altered during development; As3mt mRNA was at twice the amount in adult than in fetal stage.…”

Section: Resultsmentioning

confidence: 99%

RNA-Sequencing Quantification of Hepatic Ontogeny and Tissue Distribution of mRNAs of Phase II Enzymes in Mice

et al. 2013

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Phase II conjugating enzymes play key roles in the metabolism of xenobiotics. In the present study, RNA sequencing was used to elucidate hepatic ontogeny and tissue distribution of mRNA expression of all major known Phase II enzymes, including enzymes involved in glucuronidation, sulfation, glutathione conjugation, acetylation, methylation, and amino acid conjugation, as well as enzymes for the synthesis of Phase II cosubstrates, in male C57BL/6J mice. Livers from male C57BL/6J mice were collected at 12 ages from prenatal to adulthood. Many of these Phase II enzymes were expressed at much higher levels in adult livers than in perinatal livers, such as Ugt1a6b, -2a3, -2b1, -2b5, -2b36, -3a1, and -3a2; Gsta1, -m1, -p1, -p2, and -z1; mGst1; Nat8; Comt; Nnmt; Baat; Ugdh; and Gclc. In contrast, hepatic mRNA expression of a few Phase II enzymes decreased during postnatal liver development, such as mGst2, mGst3, Gclm, and Mat2a. Hepatic expression of certain Phase II enzymes peaked during the adolescent stage, such as Ugt1a1, Sult1a1, Sult1c2, Sult1d1, Sult2as, Sult5a1, Tpmt, Glyat, Ugp2, and Mat1a. In adult mice, the total transcripts for Phase II enzymes were comparable in liver, kidney, and small intestine; however, individual Phase II enzymes displayed marked tissue specificity among the three organs. In conclusion, this study unveils for the first time developmental changes in mRNA abundance of all major known Phase II enzymes in mouse liver, as well as their tissuespecific expression in key drug-metabolizing organs. The age-and tissue-specific expression of Phase II enzymes indicate that the detoxification of xenobiotics is highly regulated by age and cell type.

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Section: Resultsmentioning

confidence: 99%

RNA-Sequencing Quantification of Hepatic Ontogeny and Tissue Distribution of mRNAs of Phase II Enzymes in Mice

et al. 2013

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“…BORCS7 encodes BLOC‐1‐related complex subunit 7 (Diaskedin), part of the recently described BLOC‐1‐related complex, which has been implicated in lysosomal function and cell migration [Pu et al, 2015]. AS3MT encodes arsenic methyltransferase, which has a known role in arsenic metabolism [Sumi and Himeno, 2012], although its functions in the brain are currently unclear. NT5C2 encodes a cytosolic purine 5′‐nucleotidase (cytosolic 5′‐nucleotidase II, or cN‐II) involved in cellular purine metabolism [Itoh, 2013].…”

Section: Discussionmentioning

confidence: 99%

Genome‐wide significant schizophrenia risk variation on chromosome 10q24 is associated with altered cis‐regulation of BORCS7, AS3MT, and NT5C2 in the human brain

Duarte

Troakes

Nolan

et al. 2016

American J of Med Genetics Pt B

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Chromosome 10q24.32‐q24.33 is one of the most robustly supported risk loci to emerge from genome‐wide association studies (GWAS) of schizophrenia. However, extensive linkage disequilibrium makes it difficult to distinguish the actual susceptibility gene(s) at the locus, limiting its value for improving biological understanding of the condition. In the absence of coding changes that can account for the association, risk is likely conferred by altered regulation of one or more genes in the region. We, therefore, used highly sensitive measures of allele‐specific expression to assess cis‐regulatory effects associated with the two best‐supported schizophrenia risk variants (SNP rs11191419 and indel ch10_104957618_I/rs202213518) on the primary positional candidates BORCS7, AS3MT, CNNM2, and NT5C2 in the human brain. Heterozygosity at rs11191419 was associated with increased allelic expression of BORCS7 and AS3MT in the fetal and adult brain, and with reduced allelic expression of NT5C2 in the adult brain. Heterozygosity at ch10_104957618_I was associated with reduced allelic expression of NT5C2 in both the fetal and adult brain. Comparisons between cDNA ratios in heterozygotes and homozygotes for the risk alleles indicated that cis‐effects on NT5C2 expression in the adult dorsolateral prefrontal cortex could be largely accounted for by genotype at these two risk variants. While not excluding effects on other genes in the region, this study implicates altered neural expression of BORCS7, AS3MT, and NT5C2 in susceptibility to schizophrenia arising from genetic variation at the chromosome 10q24 locus. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

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“…Many people around the world are exposed to As-polluted underground water and soil and suffer from chronic As poisoning, which causes hyperkeratosis, cancer, diabetes, cardiovascular disease, and other diseases (Sumi and Himeno, 2012).…”

Section: Introductionmentioning

confidence: 99%

Arsenic redox transformation by Pseudomonas sp. HN-2 isolated from arsenic-contaminated soil in Hunan, China

Zhang

Yin

Cai

et al. 2016

Journal of Environmental Sciences

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A mesophilic, Gram-negative, arsenite[As(III)]-oxidizing and arsenate[As(V)]-reducing bacterial strain, Pseudomonas sp. HN-2, was isolated from an As-contaminated soil. Phylogenetic analysis based on 16S rRNA gene sequencing indicated that the strain was closely related to Pseudomonas stutzeri. Under aerobic conditions, this strain oxidized 92.0% (61.4 μmol/L) of arsenite to arsenate within 3 hr of incubation. Reduction of As(V) to As(III) occurred in anoxic conditions. Pseudomonas sp. HN-2 is among the first soil bacteria shown to be capable of both aerobic As(III) oxidation and anoxic As(V) reduction. The strain, as an efficient As(III) oxidizer and As(V) reducer in Pseudomonas, has the potential to impact arsenic mobility in both anoxic and aerobic environments, and has potential application in As remediation processes.

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Role of Arsenic (+3 Oxidation State) Methyltransferase in Arsenic Metabolism and Toxicity

Cited by 34 publications

References 47 publications

RNA-Sequencing Quantification of Hepatic Ontogeny and Tissue Distribution of mRNAs of Phase II Enzymes in Mice

RNA-Sequencing Quantification of Hepatic Ontogeny and Tissue Distribution of mRNAs of Phase II Enzymes in Mice

Genome‐wide significant schizophrenia risk variation on chromosome 10q24 is associated with altered cis‐regulation of BORCS7, AS3MT, and NT5C2 in the human brain

Arsenic redox transformation by Pseudomonas sp. HN-2 isolated from arsenic-contaminated soil in Hunan, China

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