4.7 Article

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

期刊

出版社

MDPI
DOI: 10.3390/ijms222111724

关键词

connexin; hemichannel; gap junction; genotoxic; non-genotoxic; carcinogen

资金

  1. European Commission (ONTOX project) [963845]
  2. Alternatives Research and Development Foundation (ARDF)
  3. Center for Alternatives to Animal Testing at Johns Hopkins University, USA (CAAT)
  4. Methusalem program of the Flemish government
  5. Research Foundation Flanders (FWO Vlaanderen) [G009514N, G010214N]
  6. Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP-FWO) [18/10953-9]
  7. University Hospital of the Vrije Universiteit Brussel-Belgium (Willy Gepts Fonds UZ-Brussel)
  8. Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [18/10953-9] Funding Source: FAPESP

向作者/读者索取更多资源

The study found that both genotoxic and non-genotoxic carcinogenic compounds negatively affect connexin32 expression, but no specific effects related to chemical type were observed at the gap junction or connexin hemichannel functionality level.
Connexin-based channels play key roles in cellular communication and can be affected by deleterious chemicals. In this study, the effects of various genotoxic carcinogenic compounds, non-genotoxic carcinogenic compounds and non-carcinogenic compounds on the expression and functionality of connexin-based channels, both gap junctions and connexin hemichannels, were investigated in human hepatoma HepaRG cell cultures. Expression of connexin26, connexin32, and connexin43 was evaluated by means of real-time reverse transcription quantitative polymerase chain reaction analysis, immunoblot analysis and in situ immunostaining. Gap junction functionality was assessed via a scrape loading/dye transfer assay. Opening of connexin hemichannels was monitored by measuring extracellular release of adenosine triphosphate. It was found that both genotoxic and non-genotoxic carcinogenic compounds negatively affect connexin32 expression. However, no specific effects related to chemical type were observed at gap junction or connexin hemichannel functionality level.

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