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

In this study we demonstrated that two polyunsaturated fatty acids, arachid onic acid (AA, n-6) and docosahexaenoic acid (DHA, n-3), modulate the secre tion of bile salt-dependent lipase (BSDL) by pancreatic AR4-2J cells. The e ffects of AA and DHA were also compared with that of the monounsaturated fa tty 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, s imilarly decreased the amount of secreted BSDL and perturbed the intracellu lar partitioning of the enzyme, whereas OA had no effect. Particularly, AA and DHA induced the retention of the enzyme in microsomes and lowered its c ontent in the cell cytosol. We have further shown that AA treatment decreas ed the ubiquitination of the protein, and consequently diminished its expor t toward the cytosol, a result that might explain the retention of BSDL in microsomes and correlated with membrane phospholipids alteration. The retai ned protein was further degraded by a nonproteasomal pathway that likely in volves ATP-dependent endoplasmic reticulum proteases.ie These findings conc erning the regulation of the pancreatic BSDL secretion by two polyunsaturat ed acids, AA and DHA, might be of physiological importance in the plasmatic and cellular cholesterol homeostasis.