Epigenetic properties of the diarrhetic marine toxin okadaic acid: inhibition of the gap junctional intercellular communication in a human intestine epithelial cell line.
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.
D018938:Caco-2 Cells; D002273:Carcinogens / Q000633:toxicity*; D002450:Cell Communication / Q000187:drug effects* / Q000235:genetics*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018031:Connexin 43 / Q000096:biosynthesis / Q000235:genetics; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects*; D019084:Fluorescent Antibody Technique, Indirect; D017629:Gap Junctions / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D007422:Intestines / Q000166:cytology / Q000187:drug effects*; D009153:Mutagens; D019319:Okadaic Acid / Q000633:toxicity*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002273:Carcinogens; D018031:Connexin 43; D018076:DNA, Complementary; D009153:Mutagens; D012333:RNA, Messenger; D019319:Okadaic Acid