Nutrient availability and lactogenic hormones regulate mammary protein synthesis through the mammalian target of rapamycin signaling pathway
Nutrient availability and lactogenic hormones regulate mammary protein synthesis through the mammalian target of rapamycin signaling pathway
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DOI：
10.3168/jds.2009-2444
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发表时间：
2010-01-01
影响因子：
3.5
通讯作者：
Cant, J. P.
中科院分区：
文献类型：
--
作者：
Burgos, S. A.;Dai, M.;Cant, J. P.
影响牛乳腺蛋白质翻译的营养和内分泌因素，以及介导其作用的分子机制，还没有得到很好的理解。本研究的目的是评估哺乳动物雷帕霉素靶蛋白（mTOR）信号通路在营养素和激素调节乳腺蛋白质合成中的作用。从泌乳奶牛中分离的乳腺上皮腺泡在培养基中单独或组合地含有AA或葡萄糖和乙酸盐（GA）的混合物作为能量底物，或催乳激素氢化可的松、胰岛素和催乳素（HIP）的组合。测量乳腺蛋白质合成速率和mTOR信号传导途径组分磷酸化状态的变化。随着培养基中AA可用性的增加，乳腺蛋白质合成增加了50%。GA的存在下，或治疗乳腺腺泡与HIP单独不影响乳腺蛋白质的合成。乳腺蛋白质合成的刺激AA增强HIP处理，但不存在GA在培养基中。用HIP处理乳腺腺泡诱导蛋白激酶B磷酸化。在培养基中添加AA或GA时，这种效应增强。AA对乳腺蛋白合成的刺激和HIP对其的增强与mTOR底物、p70核糖体蛋白S6激酶-1和真核起始因子4 E（eIF 4 E）结合蛋白-1（4 E-BP 1）的磷酸化增加以及4 E-BP 1与eIF 4 E的解离有关。结果表明，营养素和激素可能通过mTOR信号通路调节乳腺蛋白质合成。
The nutritional and endocrine factors affecting protein translation in the bovine mammary gland, and the molecular mechanisms mediating their effects, are not well understood. The objective of this study was to assess the role of the mammalian target of rapamycin (mTOR) signaling pathway in the regulation of mammary protein synthesis by nutrients and hormones. Mammary epithelial acini isolated from lactating dairy cows were treated in medium containing, alone or in combination, a mixture of AA or glucose and acetate (GA) as energy substrates, or a combination of the lactogenic hormones hydrocortisone, insulin, and prolactin (HIP). Changes in the rate of mammary protein synthesis and the phosphorylation state of components of the mTOR signaling pathway were measured. Mammary protein synthesis was 50% higher with increased availability of AA in medium. The presence of GA or treatment of mammary acini with HIP alone did not affect mammary protein synthesis. The stimulation of mammary protein synthesis by AA was enhanced by HIP treatment, but not by the presence of GA in medium. Treatment of mammary acini with HIP induced the phosphorylation of protein kinase B. This effect was augmented in the presence of either AA or GA in medium. The stimulation of mammary protein synthesis by AA and its enhancement by HIP were associated with increased phosphorylation of the mTOR substrates, p70 ribosomal protein S6 kinase-1, and eukaryotic initiation factor 4E (eIF4E)-binding protein-1 (4E-BP1), and dissociation of 4E-BP1 from eIF4E. The results suggest that nutrients and hormones may modulate mammary protein synthesis through the mTOR signaling pathway.