Nicotine affects protein complex rearrangement in Caenorhabditis elegans cells

Drug Chem Toxicol. 2017 Oct;40(4):470-483. doi: 10.1080/01480545.2016.1264411. Epub 2017 Jan 3.

Abstract

Nicotine may affect cell function by rearranging protein complexes. We aimed to determine nicotine-induced alterations of protein complexes in Caenorhabditis elegans (C. elegans) cells, thereby revealing links between nicotine exposure and protein complex modulation. We compared the proteomic alterations induced by low and high nicotine concentrations (0.01 mM and 1 mM) with the control (no nicotine) in vivo by using mass spectrometry (MS)-based techniques, specifically the cetyltrimethylammonium bromide (CTAB) discontinuous gel electrophoresis coupled with liquid chromatography (LC)-MS/MS and spectral counting. As a result, we identified dozens of C. elegans proteins that are present exclusively or in higher abundance in either nicotine-treated or untreated worms. Based on these results, we report a possible network that captures the key protein components of nicotine-induced protein complexes and speculate how the different protein modules relate to their distinct physiological roles. Using functional annotation of detected proteins, we hypothesize that the identified complexes can modulate the energy metabolism and level of oxidative stress. These proteins can also be involved in modulation of gene expression and may be crucial in Alzheimer's disease. The findings reported in our study reveal putative intracellular interactions of many proteins with the cytoskeleton and may contribute to the understanding of the mechanisms of nicotinic acetylcholine receptor (nAChR) signaling and trafficking in cells.

Keywords: Alzheimer’s disease; Nicotine; epigenetics; fatty acid metabolism; hormesis; insulin signaling; oxidative stress.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Caenorhabditis elegans / drug effects*
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Computational Biology
  • Cytoskeleton / drug effects
  • Cytoskeleton / metabolism
  • Energy Metabolism / drug effects
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental / drug effects*
  • Gene Regulatory Networks / drug effects
  • Models, Biological*
  • Molecular Sequence Annotation
  • Nicotine / toxicity*
  • Nicotinic Agonists / toxicity*
  • Osmolar Concentration
  • Oxidative Stress / drug effects*
  • Protein Multimerization / drug effects
  • Protein Transport / drug effects
  • Proteomics / methods
  • Receptors, Nicotinic / chemistry
  • Receptors, Nicotinic / metabolism
  • Signal Transduction / drug effects

Substances

  • Caenorhabditis elegans Proteins
  • Nicotinic Agonists
  • Receptors, Nicotinic
  • Nicotine