title: Diallyl disulfide (DADS) enhances gap-junctional intercellular communication by both direct and indirect mechanisms in rat liver cells.
abstract: Diallyl disulfide (DADS), a sulfur compound from garlic has been shown to exert many biological effects: induction of carcinogen detoxication, inhibition of tumor cell proliferation, etc. These effects are consistent with its anticarcinogenic properties in animal models and could account for garlic protective effects in humans. Our study demonstrates that DADS can improve gap-junctional intercellular communication (GJIC) in vitro. In rat liver epithelial cells (REL cells), using the dye transfer assay, we observe a time-dependent stimulation of GJIC by DADS at non-cytotoxic concentrations. In addition, incubation of cells with DADS for 1 h prevents the inhibition of GJIC induced by 3,5-di-tertio-butyl-4-hydroxytoluene (BHT). We have studied the direct effects of DADS on the regulation of GJIC, and especially on the expression and localization of the connexin expressed in these cells (Cx43): the enhancement of dye transfer (x1.6) by DADS from 1 to 50 micro M is associated with an increase (x1.3-1.8) in the amount of Cx43 protein (western blotting) with no alteration of its localization in the cell-cell contact regions of the plasma membrane (immunofluorescence analysis). We have also explored the possibility that DADS might act indirectly on GJIC. On one hand, DADS does not change the amount of E-cadherin, the adhesion molecule expressed in epithelial cells. On the other hand, it induces rapid inhibition of protein glycosylation. The data suggest that DADS could reduce local constraints imposed by glycoproteins, thus facilitating dye transfer. In conclusion, DADS can be included with other plant microconstituents, which have been demonstrated to improve GJIC. Its effect on REL cells can be explained by its ability to enhance the amount of Cx43 and also to diminish the level of glycosylated proteins.
authors.affiliation: Laboratoire de Nutrition et Sécurité Alimentaire, INRA, Jouy-en-Josas, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Huard
authors.forename: Nathalie
authors.initials: N
authors.lastname: Druesne
authors.forename: Denis
authors.initials: D
authors.lastname: Guyonnet
authors.forename: Muriel
authors.initials: M
authors.lastname: Thomas
authors.forename: Anthony
authors.initials: A
authors.lastname: Pagniez
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Le Bon
authors.forename: Paule
authors.initials: P
authors.lastname: Martel
authors.forename: Catherine
authors.initials: C
authors.lastname: Chaumontet
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology*; D000818:Animals; D002084:Butylated Hydroxytoluene / Q000633:toxicity; D015820:Cadherins / Q000032:analysis; D002450:Cell Communication / Q000187:drug effects*; D002478:Cells, Cultured; D018031:Connexin 43 / Q000032:analysis; D004220:Disulfides / Q000494:pharmacology*; D017629:Gap Junctions / Q000187:drug effects*; D006031:Glycosylation; D022781:Hepatocytes / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D010766:Phosphorylation; D051381:Rats
chemical_list: D000498:Allyl Compounds; D015820:Cadherins; D018031:Connexin 43; D004220:Disulfides; D002084:Butylated Hydroxytoluene; C028009:diallyl disulfide