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

Arch Toxicol. 2016 Dec;90(12):3125-3128. doi: 10.1007/s00204-016-1844-2. Epub 2016 Sep 3.

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.

Keywords: Arsenic; As3mt knockout; Liver; Mouse; Phophatidycholine; Plasma.

MeSH terms

  • Animals
  • Arsenic / pharmacokinetics
  • Arsenic / toxicity*
  • Arsenic Poisoning / blood
  • Arsenic Poisoning / enzymology*
  • Arsenic Poisoning / metabolism
  • Arsenic Poisoning / physiopathology
  • Arsenites / administration & dosage
  • Biotransformation
  • Carcinogens, Environmental / pharmacokinetics
  • Carcinogens, Environmental / toxicity*
  • Female
  • Liver / drug effects*
  • Liver / enzymology
  • Liver / metabolism
  • Male
  • Methylation / drug effects
  • Methyltransferases / genetics
  • Methyltransferases / metabolism*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neoplasms / blood
  • Neoplasms / chemically induced*
  • Neoplasms / etiology
  • Neoplasms / metabolism
  • Phosphatidylcholines / blood
  • Phosphatidylcholines / metabolism*
  • Sex Characteristics

Substances

  • Arsenites
  • Carcinogens, Environmental
  • Phosphatidylcholines
  • Methyltransferases
  • AS3MT protein, mouse
  • arsenite
  • Arsenic