Neurogenic-committed human pre-adipocytes express CYP1A isoforms

Chem Biol Interact. 2010 Mar 30;184(3):474-83. doi: 10.1016/j.cbi.2010.01.009. Epub 2010 Jan 18.

Abstract

Stem cell models offer an opportunity both for therapeutic use and for the assessment of alternative in vitro models. Human lipoaspirate is a source of adult stem cells (pre-adipocytes), which are able to differentiate into various phenotypes, such as neurogenic lineage. Here, we analyse the suitability of these in vitro models in screening exogenous compounds, such as environmental pollutants, that may affect adipose cells and neurogenic development. To evaluate neurogenic differentiation, we analysed expression of cholinergic system and acetylcholinesterase immunoreactivity. Heterocyclic derivatives of polycyclic aromatic hydrocarbons (PAHs) are often significant components of environmental contaminants. As they contain inducers of cytochrome P450 1A1 (CYP1A1), we explored the activity of CYP1A1-related enzymes, i.e. 7-ethoxycoumarin- and 7-ethoxyresorufin-O-deethylase (ECOD and EROD) in both cell systems in basal conditions and after exposure to non-cytotoxic doses of beta-naphthoflavone (BNF), a well-known PAH-type inducer. Both cell models showed basal and inducible levels of ECOD. Analysis of CYP1A1 protein expression and EROD-related enzyme activity confirmed the inducibility of the CYP1A1 isoform by BNF. These results demonstrate that mesenchymal adult stem cells can constitute innovative models. We therefore propose the use of pre-adipocytes and their neurogenic derivates to evaluate the cytotoxic/biological effects of unintended exposure to contaminants.

MeSH terms

  • 7-Alkoxycoumarin O-Dealkylase / metabolism
  • Acetyltransferases / metabolism
  • Adipocytes / cytology*
  • Adipocytes / enzymology
  • Adult Stem Cells / cytology
  • Adult Stem Cells / enzymology*
  • Cell Differentiation
  • Cytochrome P-450 CYP1A1 / metabolism*
  • Environmental Pollutants / toxicity
  • Enzyme Inhibitors / toxicity
  • Flow Cytometry
  • Humans
  • Neurons / cytology
  • Neurons / enzymology*
  • Polycyclic Aromatic Hydrocarbons / toxicity
  • Protein Isoforms / metabolism
  • beta-Naphthoflavone / toxicity

Substances

  • Environmental Pollutants
  • Enzyme Inhibitors
  • Polycyclic Aromatic Hydrocarbons
  • Protein Isoforms
  • beta-Naphthoflavone
  • 7-Alkoxycoumarin O-Dealkylase
  • Cytochrome P-450 CYP1A1
  • Acetyltransferases