Skip to main content
Log in

Knockout of arsenic (+3 oxidation state) methyltransferase results in sex-dependent changes in phosphatidylcholine metabolism in mice

  • Short Communication
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

Arsenic (+3 oxidation state) methyltransferase is the key enzyme in the methylation pathway for inorganic arsenic. We have recently shown that As3mt knockout (KO) has a profound effect on metabolomic profiles in mice. Phosphatidylcholine species (PCs) were the largest group of metabolites altered in both plasma and urine. The present study used targeted analysis to investigate the KO-associated changes in PC profiles in the liver, the site of PC synthesis. Results show that As3mt KO has a systemic effect on PC metabolism and that this effect is sex dependent.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

References

  • Antonelli R, Shao K, Thomas DJ, Sams R II, Cowden J (2014) AS3MT, GSTO, and PNP polymorphisms: impact on arsenic methylation and implications for disease susceptibility. Environ Res 132:156–167

    Article  CAS  PubMed  Google Scholar 

  • Bligh EG, Dyer WJ (1959) A rapid method for total lipid extraction and purification. Can J Biochem Physiol 37:911–917

    Article  CAS  PubMed  Google Scholar 

  • Cole LK, Vance JE, Vance DE (2012) Phosphatidylcholine biosynthesis and lipoprotein metabolism. Biochimica et Biophysica Acta (BBA) Mol Cell Biol Lipids 1821:754–761

    Article  CAS  Google Scholar 

  • Currier JM, Douillet C, Drobná Z, Stýblo M (2016) Oxidation state specific analysis of arsenic species in tissues of wild-type and arsenic (+3 oxidation state) methyltransferase-knockout mice. J Environ Sci. doi:10.1016/j.jes.2016.06.018

  • Han X, Yang K, Gross RW (2012) Multi-dimensional mass spectrometry-based shotgun lipidomics and novel strategies for lipidomic analyses. Mass Spectrom Rev 31:134–178

    Article  CAS  PubMed  Google Scholar 

  • Hermansson M, Hokynar K, Somerharju P (2011) Mechanisms of glycerophospholipid homeostasis in mammalian cells. Prog Lipid Res 50:240–257

    Article  CAS  PubMed  Google Scholar 

  • Huang MC, Douillet C, Su M, Zhou K, Wu T, Chen W, Galanko JA, Drobná Z, Saunders RJ, Martin E et al (2016) Metabolomic profiles of arsenic (+3 oxidation state) methyltransferase knockout mice: effect of sex and arsenic exposure. Arch Toxicol. doi:10.1007/s00204-016-1676-0

  • Hughes M, Edwards B, Herbin-Davis K, Saunders J, Styblo M, Thomas D (2010) Arsenic (+3 oxidation state) methyltransferase genotype affects steady-state distribution and clearance of arsenic in arsenate-treated mice. Toxicol Appl Pharmacol 249:217–223

    Article  CAS  PubMed  Google Scholar 

  • Robins S, Fasulo J, Robins V, Patton G (1991) Utilization of different fatty acids for hepatic and biliary phosphatidylcholine formation and the effect of changes in phosphatidylcholine molecular species on biliary lipid secretion. J Lipid Res 32:985–992

    CAS  PubMed  Google Scholar 

  • Simons B, Kauhanen D, Sylvänne T, Tarasov K (2012) Shotgun lipidomics by sequential precursor ion fragmentation on a hybrid quadrupole time-of-flight mass spectrometer. Metabolites 2:195–213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thomas DJ, Li J, Waters SB, Xing W, Adair BM, Drobna Z, Devesa V, Styblo M (2007) Arsenic (+3 oxidation state) methyltransferase and the methylation of arsenicals. Exp Biol Med (Maywood) 232:3–13

    CAS  Google Scholar 

  • Vance D (2008) Role of phosphatidylcholine biosynthesis in the regulation of lipoprotein homeostasis. Curr Opin Lipidol 19:229–234

    Article  CAS  PubMed  Google Scholar 

  • Watanabe T, Hirano S (2013) Metabolism of arsenic and its toxicological relevance. Arch Toxicol 87:969–979

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Drs. Robert Murphy and Karin Zemski Berry at the University of Colorado Lipidomics Core for conducting the hepatic PC analysis.

Funding

This work was supported by the National Institute of Environmental Health Sciences through Grants Nos. 1R01ES022697 and T32 ES007126.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Miroslav Stýblo.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 670 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Huang, M.C., Douillet, C.C. & Stýblo, M. Knockout of arsenic (+3 oxidation state) methyltransferase results in sex-dependent changes in phosphatidylcholine metabolism in mice. Arch Toxicol 90, 3125–3128 (2016). https://doi.org/10.1007/s00204-016-1844-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00204-016-1844-2

Keywords

Navigation