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Epigenetic properties of the diarrhetic marine toxin okadaic acid: inhibition of the gap junctional intercellular communication in a human intestine epithelial cell line

  • Genotoxicity
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Abstract

Okadaic acid (OA) is produced by several types of dinoflagellates (marine plankton) and has been implicated as the causative agent of diarrhetic shellfish syndrome. Previous studies have shown that okadaic acid is a tumor promoter and a specific potent inhibitor of protein phosphatases and protein synthesis. These effects in turn affect intracellular processes such as metabolism, contractility, gene transcription, and the maintenance of cytoskeletal structure. Gap junctional intercellular communication (GJIC) is a means of maintaining cellular homeostasis in organs, the disruption of which favors tumor cell growth. The GJIC involves the transfer of small water-soluble molecules through intercellular channels (gap junctions), composed of proteins called connexins. OA disrupts cellular homeostasis in Caco-2 cells through several mechanisms including protein synthesis inhibition, apoptosis, and clastogenic effects. The aim of this study was then to evaluate the expression of the connexin 43 (Cx 43) mRNA in relation with the cytotoxicity induced by OA (3.75–60 ng/ml) in a human colonic epithelial cell line in culture (Caco-2 cells). OA produced a dose-dependent inhibition of GJIC in Caco-2 cells, along with a parallel decrease in the expression of Cx 43 as shown by immunohistochemistry using anti-Cx 43 antibody. Since Cx 43 is implicated in the suppression of tumors and OA is a tumor promoter, the inhibition of GJIC may play an important role in its carcinogenesis. These data are discussed in relation to the toxicity of OA, total RNA synthesis, and possible specificity of Cx 43 inhibition in the GJIC.

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Fig. 1A, B.
Fig. 2A, B.
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Fig. 4A, B.

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Abbreviations

Cx:

Connexin

OA:

Okadaic acid

MTS:

2-(p-iodophenyl)-3-p-3-nitrophenyl-5-phenyltetrazolium

GJIC:

Gap junctional intracellular communication

DMEM:

Dulbecco's modified Eagle medium

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

cDNA:

Complementary DNA

mRNA:

Messenger RNA

RT-PCR:

Reverse transcription polymerase chain reaction

PBS:

Phosphate-buffered saline

BSA:

Bovine serum albumin

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Acknowledgements

The study described was supported in part by the French Institute of Marine Research (IFREMER), 1 Quai du Commandant Silhouette, 33120 Arcachon (IFREMER, PNEAT, n° 96-5 411452, 1996) France, University Bordeaux 2, France. The authors are grateful to the French National Academy of Medicine for the award of Elisabeth Taub to Professor E.E. Creppy.

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Authors and Affiliations

  1. Laboratory of Toxicology and Applied Hygiene, University Victor Segalen Bordeaux 2, 146, rue Léo-Saignat, 33076 , Bordeaux, France

    Adama Traoré, Isabelle Baudrimont & Edmond Ekue Creppy

  2. Faculty of Pharmacy, University of Abidjan, Abidjan, Ivory Coast

    Sebastien Dano

  3. Faculty of Sciences and Technology, Cotonou, Benin

    Ambaliou Sanni

  4. Laboratory of Cellular Biochemistry, Catholic University of Louvain, Louvain, Belgium

    Yvan Larondelle & Yves Jacques Schneider

Authors
  1. Adama Traoré
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  2. Isabelle Baudrimont
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  3. Sebastien Dano
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  4. Ambaliou Sanni
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  5. Yvan Larondelle
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  6. Yves Jacques Schneider
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  7. Edmond Ekue Creppy
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Correspondence to Edmond Ekue Creppy.

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Traoré, A., Baudrimont, I., Dano, S. et al. Epigenetic properties of the diarrhetic marine toxin okadaic acid: inhibition of the gap junctional intercellular communication in a human intestine epithelial cell line. Arch Toxicol 77, 657–662 (2003). https://doi.org/10.1007/s00204-003-0460-0

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  • DOI: https://doi.org/10.1007/s00204-003-0460-0

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