GSK3β调节奶牛乳腺上皮细胞乳蛋白和乳脂肪合成

张霞 赵锋 黄玉玲 李庆章 高学军

摘 要：GSK3β为AKT1下游信号分子，受PI3K/AKT调控。GSK3β磷酸化后被抑制，通过调节下游分子elF2B等促进乳蛋白合成。mTOR在调节乳蛋白合成中发挥重要作用，近来发现GSK3β和mTORC1均可通过调节SREBP1促进乳脂合成。但尚不清楚GSK3β和mTORC1在调节乳蛋白和乳脂合成方面的相互作用关系。该研究通过对GSK3β进行超表达和抑制，观察其对体外培养的奶牛乳腺上皮细胞细胞增殖、乳蛋白和乳脂肪合成的影响，及对mTOR途径的影响。结果发现GSK3β是奶牛乳腺上皮细胞细胞增殖、乳蛋白和乳脂肪合成的负调控分子，通过抑制mTORC1发挥作用。蛋氨酸可以抑制GSK3β和激活mTORC1，促进细胞增殖、乳蛋白和乳脂肪合成。该研究结果进一步揭示了GSK3β在奶牛乳腺上皮细胞细胞增殖、乳蛋白和乳脂肪合成中的负调控分子机理。

关键词：糖原合成酶激酶3β 奶牛乳腺上皮细胞 mTOR SREBP1 乳蛋白 乳脂肪

GSK3β Regulates Milk Protein and Fat Synthesis in Dairy Cow Mammary Epithelial Cells in Vitro

Zhang Xia Zhao Feng Huang Yuling Li Qingzhang Gao Xuejun

（Northeast Agricultural University）

Abstract：GSK3β acting as the downstream of AKT1， its activity is regulated by activation of the PI3K/AKT survival pathway and inhibitory phosphorylation of GSK3β can regulate in turn through phosphorylation of several proteins （such as elF2B） to promote protein synthesis. In addition， mTOR pathway also can regulate protein synthesis and recent studies have found that both GSK3β and mTORC1 can regulate SREBP1 to promote fat synthesis. However， so far， the cross talk between GSK3β and the mTOR pathway in dairy cow mammary epithelial cells （DCMECs） to regulate milk protein and fat synthesis is not well known. In this study we constructed transfected DCMECs with GSK3β and its inhibitor in order to analyze the expression and localization of GSK3β and the function in transfected DCMECs by CASY， fluorescent immunostaining， western blotting. Overexpression and inhibition experiments showed that the inactivity of GSK3β promoted proliferation and upregulated milk protein and fat synthesis through mTOR pathway in DCMECs. Furthermore， methionine （Met） could enhance this action， Met and Licl （Lithium Chloride， a GSK3β inhibitor） can coordinate together to promote protein synthesis. These ？ndings that GSK3β involves in regulation of milk synthesis shed new insights for understanding the mechanisms of milk protein and fat synthesis.

Key Words：Glycogen synthase kinase 3β； Dairy cow mammary epithelial cells； mTOR； SREBP1； Milk protein； Milk fat

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