Ethanol impairs the assembly and disassembly of actin cytoskeleton and cell adhesion via the RhoA signaling pathway, catenin p120 and E-cadherin in CCK-stimulated pancreatic acini.
The purpose of the present study was to evaluate the effects of EtOH on RhoA, actin cytoskeleton, catenin p120 and E-cadherin and their interactions in CCK-stimulated rat pancreatic acini. In isolated rat pancreatic acinar cells, CCK stimulation enhanced protein expression and association of RhoA, G(α13), Vav-2, catenin p120 and E-cadherin. CCK induced translocation and activation of RhoA and actin-filamentous assembly and disassembly. RhoA was diffusely localized throughout the acinar cell in the resting state and redistributed to the apical site in response to submaximal CCK stimulation and to a lesser extent in response to supramaximal CCK stimulation. Ethanol and subsequent submaximal CCK stimulation mimicked the effect of supramaximal CCK stimulation in terms of amylase secretion and morphologic effects. However, inhibition of RhoA translocation and activation were observed only with ethanol pretreatment. Ethanol followed by supramaximal CCK stimulation disrupted the well-defined localization of catenin p120 and E-cadherin around the lateral plasma membrane. These data suggest that ethanol impaired the assembly and disassembly of actin cytoskeleton and impaired cell-cell adhesion via the RhoA signaling pathways, catenin p120 and E-cadherin in CCK-stimulated pancreatic acini.
Division of Gastroenterology, Department of Medicine, Showa University School of Medicine, Tokyo 142-8666, Japan.
Tomoyuki
T
Iwata
Fumihiko
F
Nozu
Michio
M
Imawari
D000199:Actins / Q000378:metabolism*; D000818:Animals; D051177:Catenins / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D055292:Pancreatic alpha-Amylases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012844:Sincalide / Q000494:pharmacology; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*; D000095002:Delta Catenin
D000199:Actins; D051177:Catenins; D000431:Ethanol; D055292:Pancreatic alpha-Amylases; D020742:rhoA GTP-Binding Protein; D012844:Sincalide; D000095002:Delta Catenin