期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 21, 页码 -出版社
MDPI
DOI: 10.3390/ijms222111724
关键词
connexin; hemichannel; gap junction; genotoxic; non-genotoxic; carcinogen
资金
- European Commission (ONTOX project) [963845]
- Alternatives Research and Development Foundation (ARDF)
- Center for Alternatives to Animal Testing at Johns Hopkins University, USA (CAAT)
- Methusalem program of the Flemish government
- Research Foundation Flanders (FWO Vlaanderen) [G009514N, G010214N]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP-FWO) [18/10953-9]
- University Hospital of the Vrije Universiteit Brussel-Belgium (Willy Gepts Fonds UZ-Brussel)
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [18/10953-9] Funding Source: FAPESP
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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