|
KMID : 0043320070300030337
|
|
Archives of Pharmacal Research
2007 Volume.30 No. 3 p.337 ~ p.343
|
|
|
Inhibitory Effect of Bisphenol A on Gap Junctional Intercellular Communication in an Epithelial Cell line of Rat Mammary
|
|
Lee In-Kyoung
Rhee Seung-Keun
|
|
|
Abstract
|
|
|
|
An endocrine disruptor, bisphenol-A (BPA), has been reported to have several short-term actions in various cells and tissues. However, the mechanisms of these actions have not been fully elucidated. In order to assess the effect of BPA on the intercellular communication mediated by gap junctions, we conducted the present study in the rat epithelium-derived BICRM1Rk cell-line, in which connexin 43 (Cx43) is a major gap junction channel-forming protein. The cytotoxicity of BPA toward the cultured cells was evaluated by using both MTT reduction and LDH leakage assay systems. The results showed no appreciable loss in cell viability in the presence of increasing concentrations of BPA (from 0.1 to 3.2 킡) for 1 h incubation. However, most of cell viability was lost when cells were incubated for 24 hr with the same concentrations of BPA. The BPA acted as an antagonist on gap junction-mediated intercellular communication (GJIC), and the phenomenon was dose-dependent and irreversible. According to the data obtained from scrape-loading dye-transfer experiments, three quarters of normal GJIC was reduced by concentration of 0.4 킡 BPA for 1 h incubation. To identify the relevance of this retardation upon BPA treatment, the GJIC to Cx43 synthesis, the mRNA and protein levels of Cx43 were assessed with RT-PCR and Western-blotting, respectively. The total protein level of Cx43 was almost constant in a wide range of BPA concentrations, as well as in Cx43 mRNA level. These results suggest that BPA inhibits GJIC through a modulation of the gating of gap junction channels, not through a genomic modulation of Cx43.
|
|
|
KEYWORD
|
|
|
Gap junctional intercellular communication (GJIC), MTT, LDH, Scrape-loading dye transfer, Connexin 43
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
  
|
|