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Connexin-Based Channel Activity Is Not Specifically Altered by Hepatocarcinogenic Chemicals

Kaat Leroy1, Alanah Pieters1, Axelle Cooreman1

  • 1Entity of In Vitro Toxicology and Dermato-Cosmetology, Department of Pharmaceutical and Pharmacological Sciences, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.

International Journal of Molecular Sciences
|November 13, 2021
PubMed

Insights

Carcinogenic compounds negatively impact connexin32 expression in human liver cells. However, chemical type did not affect connexin-based channel function, including gap junctions and hemichannels.

Area of Science:

  • Cellular Biology
  • Toxicology
  • Biochemistry

Background:

  • Connexin-based channels are crucial for cell-to-cell communication.
  • These channels can be disrupted by harmful chemicals.
  • Understanding these effects is vital for assessing chemical toxicity.

Purpose of the Study:

  • To investigate the impact of genotoxic, non-genotoxic carcinogenic, and non-carcinogenic compounds on connexin expression and function.
  • To analyze effects on gap junctions and connexin hemichannels in human hepatoma HepaRG cells.

Main Methods:

  • Real-time RT-qPCR, immunoblotting, and immunostaining for connexin expression (Cx26, Cx32, Cx43).
  • Scrape loading/dye transfer assay for gap junction functionality.
  • Measurement of extracellular ATP release for connexin hemichannel activity.

Main Results:

  • Both genotoxic and non-genotoxic carcinogens reduced connexin32 expression.
  • No significant chemical-specific effects were observed on gap junction or connexin hemichannel function.

Conclusions:

  • Carcinogenic compounds, regardless of genotoxicity, can downregulate connexin32 expression.
  • Connexin channel functionality appears resilient to the tested chemical exposures at the functional level.
Keywords:
carcinogenconnexingap junctiongenotoxichemichannelnon-genotoxic

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