Sans Maria Dolors, Tashiro Mitsuo, Vogel Nancy L, Kimball Scot R, D'Alecy Louis G, Williams John A
Department of Cellular and Molecular Physiology, Penn State College of Medicine, Hershey, PA 17033, USA.
J Nutr. 2006 Jul;136(7):1792-9. doi: 10.1093/jn/136.7.1792.
Feeding stimulates pancreatic digestive enzyme synthesis at the translational level, and this is thought to be mediated by hormones and neurotransmitters. However, BCAAs, particularly leucine, stimulate protein synthesis in several tissues. We investigated whether BCAA stimulated the translational machinery in murine pancreas and whether their effects were independent of hormones. Rats and mice were administered (i.g. gavage) individual BCAA at 1.35 mg/g (body weight) and rat isolated pancreatic acini were incubated with BCAA under different conditions. Activation of translation initiation factors and total protein synthesis were analyzed. BCAA gavage stimulated the phosphorylation of the initiation factor 4E (eIF4E) binding protein 1 (4E-BP1) and the ribosomal protein S6 kinase (S6K), with leucine being the most effective. Leucine also increased the association of the initiation factors eIF4E and eIF4G, but did not affect the activity of the guanine nucleotide exchange factor eIF2B, nor total protein synthesis. BCAA acted independently of insulin signaling on isolated pancreatic acini from diabetic rats. The ability of leucine to promote phosphorylation of 4E-BP1 and S6K as well as enhance the assembly of the eIF4F complex was unimpaired in CCK-deficient mice. Finally, rapamycin (0.75 mg/kg) administered to rats 2 h before leucine gavage inhibited the phosphorylation of S6 and 4E-BP1 induced by leucine. We conclude that leucine may participate, as a signal as well as a substrate, in activating the translational machinery in pancreatic acinar cells independently of hormonal effects and that this action is through the mTOR pathway.
进食在翻译水平上刺激胰腺消化酶的合成，这被认为是由激素和神经递质介导的。然而，支链氨基酸（BCAAs），尤其是亮氨酸，能刺激多个组织中的蛋白质合成。我们研究了BCAAs是否刺激小鼠胰腺中的翻译机制，以及它们的作用是否独立于激素。给大鼠和小鼠经口灌胃给予1.35 mg/g（体重）的单个BCAAs，并在不同条件下用BCAAs孵育大鼠分离的胰腺腺泡。分析翻译起始因子的激活和总蛋白质合成。经口灌胃BCAAs刺激起始因子4E（eIF4E）结合蛋白1（4E-BP1）和核糖体蛋白S6激酶（S6K）的磷酸化，其中亮氨酸最为有效。亮氨酸还增加了起始因子eIF4E和eIF4G的结合，但不影响鸟嘌呤核苷酸交换因子eIF2B的活性，也不影响总蛋白质合成。BCAAs对糖尿病大鼠分离的胰腺腺泡的作用独立于胰岛素信号传导。在缺乏胆囊收缩素（CCK）的小鼠中，亮氨酸促进4E-BP1和S6K磷酸化以及增强eIF4F复合物组装的能力未受损害。最后，在给大鼠亮氨酸灌胃前2小时给予雷帕霉素（0.75 mg/kg）可抑制亮氨酸诱导的S6和4E-BP1的磷酸化。我们得出结论，亮氨酸可能作为一种信号以及底物，独立于激素作用激活胰腺腺泡细胞中的翻译机制，并且这种作用是通过雷帕霉素靶蛋白（mTOR）途径实现的。
