Effects of ethanol on the expression and secretion of bile salt-dependent lipase by pancreatic AR4-2J cells

• Published in: Biochimica et biophysica acta Vol. 1408; no. 1; pp. 44 - 54
• Main Authors: Le Petit-Thevenin, Josette, Pasqualini, Eric, Nobili, Odette, Vérine, Alain, Lombardo, Dominique
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 22.10.1998
• Subjects: Alcohol; Animals; Bile salt-dependent lipase; Dose-Response Relationship, Drug; Ethanol - pharmacology; Expression; Gene Expression Regulation, Enzymologic - drug effects; Gene Expression Regulation, Neoplastic - drug effects; Pancreas; Pancreas - enzymology; Pancreatic Neoplasms; Pyrazoles - pharmacology; Rats; RNA, Messenger - metabolism; Sterol Esterase - biosynthesis; Sterol Esterase - genetics; Transcription, Genetic - drug effects; Tumor Cells, Cultured; FAEE, fatty acid ethyl ester; CE, cholesteryl ester; Expression; Alcohol; Bile salt-dependent lipase; Apo, apolipoprotein; Pancreas; HDL, high-density lipoprotein; LDL, low-density lipoprotein; BSDL, bile salt-dependent lipase (EC 3.1.1.-)
• ISSN: 0925-4439; 0006-3002; 1879-260X
• DOI: 10.1016/S0925-4439(98)00054-4

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.