Glyphosate and AMPA Induce Alterations in Expression of Genes Involved in Chromatin Architecture in Human Peripheral Blood Mononuclear Cells (In Vitro)

Int J Mol Sci. 2021 Mar 15;22(6):2966. doi: 10.3390/ijms22062966.

Abstract

We have determined the effect of glyphosate and aminomethylphosphonic acid (AMPA) on expression of genes involved in chromatin architecture in human peripheral blood mononuclear cells (PBMCs). The cells were incubated with glyphosate and AMPA in the concentrations ranging from 0.5 to 100 μM and from 0.5, to 250 μM, respectively. The expression profile of the following genes by quantitative Real-Time PCR was evaluated: Genes involved in the DNA methylation (DNMT1, DNMT3A) and DNA demethylation process (TET3) and those involved in chromatin remodeling: genes involved in the modification of histone methylation (EHMT1, EHMT2) and genes involved in the modification of histone deacetylation (HDAC3, HDAC5). Gene profiling showed that glyphosate changed the expression of DNMT1, DMNT3A, and HDAC3, while AMPA changed the expression of DNMT1 and HDAC3. The results also revealed that glyphosate at lower concentrations than AMPA upregulated the expression of the tested genes. Both compounds studied altered expression of genes, which are characteristic for the regulation of transcriptionally inactive chromatin. However, the unknown activity of many other proteins involved in chromatin structure regulation prevents to carry out an unambiguous evaluation of the effect of tested xenobiotics on the studied process. Undoubtedly, we have observed that glyphosate and AMPA affect epigenetic processes that regulate chromatin architecture.

Keywords: AMPA; chromatin structure; epigenetics; glyphosate; human peripheral blood mononuclear cells.

MeSH terms

  • Chromatin / drug effects*
  • Chromatin / genetics
  • DNA (Cytosine-5-)-Methyltransferase 1 / genetics*
  • DNA (Cytosine-5-)-Methyltransferases / genetics*
  • DNA Methylation / drug effects
  • DNA Methyltransferase 3A
  • Dioxygenases / genetics*
  • Epigenesis, Genetic / genetics
  • Gene Expression Regulation / drug effects*
  • Glycine / analogs & derivatives
  • Glycine / pharmacology
  • Glyphosate
  • Herbicides
  • Histocompatibility Antigens / genetics
  • Histone Deacetylases / genetics
  • Histone-Lysine N-Methyltransferase / genetics
  • Humans
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Reactive Oxygen Species / metabolism
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology

Substances

  • Chromatin
  • DNMT3A protein, human
  • Herbicides
  • Histocompatibility Antigens
  • Reactive Oxygen Species
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • TET3 protein, human
  • Dioxygenases
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A
  • DNMT1 protein, human
  • EHMT2 protein, human
  • Histone-Lysine N-Methyltransferase
  • HDAC5 protein, human
  • Histone Deacetylases
  • Glycine