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首页> 外文期刊>Journal of Lipid Research >Effects of arachidonic and docosahexaenoic acids on secretion and degradation of bile salt-dependent lipase in AR4-2J cells.
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Effects of arachidonic and docosahexaenoic acids on secretion and degradation of bile salt-dependent lipase in AR4-2J cells.

机译：花生四烯酸和二十二碳六烯酸对AR4-2J细胞胆汁盐依赖性脂肪酶分泌和降解的影响。

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摘要

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.
机译：在这项研究中，我们证明了两种多不饱和脂肪酸，花生四烯酸（AA，n-6）和二十二碳六烯酸（DHA，n-3），可调节胰腺AR4-2J细胞分泌胆汁盐依赖性脂肪酶（BSDL）。还比较了AA和DHA的作用与单不饱和脂肪酸油酸（OA）的作用。我们的结果表明，用AA或DHA长期处理细胞不会影响BSDL的生物合成速率，同样会减少BSDL的分泌量并扰乱酶的细胞内分配，而OA则没有效果。特别地，AA和DHA诱导了酶在微粒体中的保留并降低了其在细胞质中的含量。我们进一步表明，AA处理降低了蛋白质的泛素化，因此减少了其向细胞质的输出，这一结果可能解释了BSDL在微粒体中的保留并与膜磷脂的改变有关。保留的蛋白质通过可能涉及ATP依赖性内质网蛋白酶的非蛋白酶体途径进一步降解。这些有关通过两种多不饱和酸（AA和DHA）调节胰腺BSDL分泌的发现可能对血浆和细胞胆固醇的体内平衡具有重要的生理意义。

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