title: Inhibitory mechanism of dimercaptopropanesulfonic acid (DMPS) in the cellular biomethylation of arsenic.
abstract: Dimercaptopropanesulfonic acid (DMPS) has been approved for the treatment of arsenic poisoning through promoting arsenic excretion and modulating arsenic species. To clarify how DMPS regulates the excretion of arsenic species, we investigated the effects of DMPS on the biomethylation of arsenite (As(3+)) in HepG2 cells. In the experiments, we found that DMPS at low concentrations dramatically decreased the content of arsenic in HepG2 cells and inhibited the cellular methylation of As(3+). Three aspects, the expression of human arsenic (III) methyltransferase (hAS3MT), the accumulation of cellular reactive oxygen species (ROS) and the in vitro enzymatic methylation of arsenic, were considered to explain the reasons for the inhibition of DMPS in arsenic metabolism. The results suggested that DMPS competitively coordinated with As(3+) and monomethylarsonous acid (MMA(3+)) to inhibit the up-regulation of arsenic on the expression of hAS3MT and block arsenic involving in the enzymatic methylation. Moreover, DMPS eliminated arsenic-induced accumulation of ROS, which might contribute to the antidotal effects of DMPS on arsenic posing.
authors.affiliation: State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, PR China.
authors.forename: Shuping
authors.initials: S
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, PR China.
authors.forename: Nan
authors.initials: N
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, PR China.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Geng
authors.affiliation: State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, PR China.
authors.forename: Xiangli
authors.initials: X
authors.lastname: Li
authors.affiliation: The Modern Analysis Center, Nanjing University, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, PR China. Electronic address: wangzl@nju.edu.cn.
authors.forename: Zhilin
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000931:Antidotes / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001151:Arsenic / Q000378:metabolism*; D020261:Arsenic Poisoning / Q000378:metabolism / Q000517:prevention & control*; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008745:Methylation / Q000187:drug effects; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D009942:Organometallic Compounds / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014494:Unithiol / Q000494:pharmacology*
chemical_list: D000931:Antidotes; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; C406082:monomethylarsonous acid; D014494:Unithiol; D008780:Methyltransferases; D001151:Arsenic
keywords: Arsenic; Biomethylation; DMPS; Inhibition; Mechanism