Silica nanoparticles disrupt OPT-2/PEP-2-dependent trafficking of nutrient peptides in the intestinal epithelium

Nanotoxicology. 2019 Oct;13(8):1133-1148. doi: 10.1080/17435390.2019.1643048. Epub 2019 Aug 9.

Abstract

Despite of the increasing application of silica nanoparticles and identification of oral exposure as a major entry portal, we lack understanding of nanosilica effects in the gut. Thus, we investigated biointeractions of nanosilica with single intestinal cells. The invertebrate nematode Caenorhabditis elegans was chosen as model organism with a tractable intestine and realistic target organism of nanomaterials in the environment. We found that nanosilica impairs the intestinal uptake of oligopeptides. Downstream to absorption by the apical OPT-2/PEP-2 transporter dipeptides were trapped in aberrant vesicles that grow over time and reach diameters of ≥6 μm. The peptide vesicles do not correspond to known organelles such as gut granules and form independently of related gene products GLO-1 or GLO-3. Formation of aberrant peptide vesicles also occurred independently of insulin/IGF-I receptor (DAF-2) signaling and daf-2 loss of function mutants showed specific vesicle patterns including distinct localization along the apical membrane of single intestinal cells. As malnutrition of exposed C. elegans manifested in reduced growth and a petite phenotype similar to OPT-2/PEP-2 transporter deficient mutants, we conclude that nanosilica-induced peptide vesicles represent a new compartment of di- and tripeptide trapping which disrupts hydrolysis of nutrient peptides and metabolism.

Keywords: Endocytosis; epithelium; food supplements; gut–brain axis; intestine; metabolism; neurotoxicology; nutrition; protein homeostasis; silica nanoparticles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / cytology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Epithelial Cells / drug effects*
  • Gene Expression Regulation / drug effects
  • Intestinal Mucosa / cytology
  • Mutation
  • Nanoparticles / chemistry
  • Nanoparticles / toxicity*
  • Protein Transport / drug effects*
  • Protein Transport / physiology
  • Silicon Dioxide / chemistry
  • Silicon Dioxide / toxicity*

Substances

  • Caenorhabditis elegans Proteins
  • Silicon Dioxide