猪乳腺V-ATPase/mTORC1信号通路的基因表达及营养调控

项目名称： 猪乳腺V-ATPase/mTORC1信号通路的基因表达及营养调控

项目编号： No.31472109

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 畜牧学与草地科学

项目作者： 方正锋

作者单位： 四川农业大学

项目金额： 88万元

中文摘要： mTORC1是哺乳动物细胞调节代谢和生长的枢纽。V-ATPase是迄今发现位于氨基酸下游并通过其活性调节mTORC1的第一个靶标。在氧化环境下，V-ATPase的半胱氨酸残基形成二硫键导致V-ATPase可逆失活，预示了V-ATPase/mTORC1应对氧化应激的潜在作用。母猪妊娠后期和哺乳期机体大量分解代谢引发氧化应激，损害乳产量，但其机制并不清楚。本项目以不同生理阶段的母猪为对象，采用现代基因组学、代谢组学和生物信息学等技术，研究mTORC1信号通路与乳腺发育、机体代谢和营养供给的相互关系；进一步以乳腺细胞为模型，研究氧化应激对V-ATPase/mTORC1的抑制效应，探索不同蛋氨酸源对V-ATPase活性及mTORC1通路的调节作用。本研究意义在于从动物整体、细胞和分子三个层面揭示乳腺mTORC1信号通路的表达调控机制，为乳腺生长发育、合成代谢和抗应激力的调控提供新的思路和理论依据。

中文关键词： 猪；乳腺；mTOR信号通路；基因表达；营养调控

英文摘要： The mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway plays a key role in regulating cellular metabolism and growth. Vacuolar H+-ATPase (V-ATPase) is the first downstream target discovered thus far in activation of mTORC1 by amino acids. Oxidizing agents result in reversible inactivation of V-ATPase activity through disulfide bond formation between cysteine residues of V-ATPase, which suggests the potential role of V-ATPase/mTORC1 in dealing with oxidative stress. It has been demonstrated that sows are under severe catabolic status during late gestation and lactation causing increased oxidative stress and impaired milk production, however, little is known about the underlying mechanism. In this study, sows in different physiological stages are used to determine the mutual relations of mTORC1 pathway signaling to mammary growth, organic metabolism and nutrition status, through modern genomics, metabolomics and bioinformatics techniques. Swine mammary epithelial cells are further used to investigate the inhibition effect of oxidative stress on V-ATPase activity and mTORC1 activation, and to test the potential modulation effect of methionine sources on V-ATPase activity and mTORC1 activation. Through this study it may reveal from the whole animal, cellular and molecular basis the mechanism of expression and manipulation of mTORC1 pathway signaling in the mammary glands, which may provide a new ideal and theory basis for the manipulation of mammary growth, anabolism and anti-stress capacity.

英文关键词： Pig;Mammary glands;mTOR signaling;Gene expression;Nutritional manipulation