J. Lipid Res.
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Journal of Lipid Research, Vol. 42, 1220-1230, August 2001
Copyright © 2001 by Lipid Research, Inc.


Original Article

Effects of arachidonic and docosahexaenoic acids on secretion and degradation of bile salt-dependent lipase in AR4-2J cells

Josette Le Petit-Thévenina, Nadine Bruneaua, Alain Ngangaa, Dominique Lombardoa, and Alain Vérinea
a INSERM Unité 559, Faculté de Médecine-Timone, 27 Bld Jean Moulin, 13385 Marseille Cedex 05, France

Correspondence to: Dominique Lombardo, To whom correspondence should be addressed., Dominique.Lombardo{at}medicine.univ-mrs.fr (E-mail)

In this study we demonstrated that two polyunsaturated fatty acids, arachidonic acid (AA, n;–6) and docosahexaenoic acid (DHA, n;–3), modulate the secretion of bile salt-dependent lipase (BSDL) by pancreatic AR4-2J cells. The effects of AA and DHA were also compared with that of the monounsaturated fatty acid, oleic acid (OA). Our results showed that the chronic treatment of cells with AA or DHA, that did not affect the biosynthesis rate of BSDL, similarly decreased the amount of secreted BSDL and perturbed the intracellular partitioning of the enzyme, whereas OA had no effect. Particularly, AA and DHA induced the retention of the enzyme in microsomes and lowered its content in the cell cytosol. We have further shown that AA treatment decreased the ubiquitination of the protein, and consequently diminished its export toward the cytosol, a result that might explain the retention of BSDL in microsomes and correlated with membrane phospholipids alteration. The retained protein was further degraded by a nonproteasomal pathway that likely involves ATP-dependent endoplasmic reticulum proteases.

These findings concerning the regulation of the pancreatic BSDL secretion by two polyunsaturated acids, AA and DHA, might be of physiological importance in the plasmatic and cellular cholesterol homeostasis. — Le Petit-Thévenin, J., N. Bruneau, A. Nganga, D. Lombardo, and A. Vérine. Effects of arachidonic and docosahexaenoic acids on secretion and degradation of bile salt-dependent lipase in AR4-2J cells. J. Lipid Res. 2001 42: 1220–1230.

Supplementary key words: oleic acid, ubiquitin, proteolytic degradation


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