Effects of ethanol on the expression and secretion of bile salt-dependent lipase by pancreatic AR4-2J cells.
The mechanisms by which ethanol administration alters pancreatic function are unknown. We have evaluated the effects of chronic ethanol treatment on secretion of a digestive enzyme: the bile salt-dependent lipase (BSDL), by the rat pancreatic cell line AR4-2J (as a model). We report that ethanol (50-300 mM) in culture medium induced a rise, in secreted and intracellular BSDL, that was a function of the duration of treatment and of the ethanol concentration. This effect was not abolished by pyrazole, which suggests a direct effect of ethanol. We have further established that the increase of BSDL activity was due to an enhanced biosynthesis of the enzyme consecutive to a major steady-state level of mRNA encoding BSDL. Also, the subcellular localization showed a specific accumulation of BSDL in the cytosolic fraction of cells chronically treated with ethanol. Given the enzymatic properties of BSDL, all these data could have some physiological consequences regarding the digestive function, plasma lipid metabolism and intracellular cholesterol homeostasis.
INSERM U260, Faculté de Médecine-Timone, 27 Blv. Jean Moulin, 13385 Marseille Cedex 5, France.
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J
Le Petit-Thevenin
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E
Pasqualini
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O
Nobili
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A
Vérine
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D
Lombardo
D000818:Animals; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D010179:Pancreas / Q000201:enzymology; D010190:Pancreatic Neoplasms; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D002787:Sterol Esterase / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D011720:Pyrazoles; D012333:RNA, Messenger; D000431:Ethanol; C031280:pyrazole; C054784:bile salt-stimulated lipase; D002787:Sterol Esterase