State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, PR China.
Milk Risk Assessment Laboratory of Ministry of Agriculture, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, PR China.
Sci Rep. 2018 Mar 2;8(1):3912. doi: 10.1038/s41598-018-22208-w.
Amino acids (AA) are one of the key nutrients that regulate cell proliferation and casein synthesis in cow mammary epithelial cells (CMEC), but the mechanism of this regulation is not yet clear. In this study, the effect of SESN2 on AA-mediated cell proliferation and casein synthesis in CMEC was assessed. After 12 h of AA starvation, CMECs were cultured in the absence of all AA (AA-), in the presences of only essential AA (EAA+), or of all AA (AA+). Cell proliferation, casein expression, and activation of the mammalian target of rapamycin complex 1 (mTORC1) pathway were increased; but SESN2 expression was decreased in response to increased EAA or AA supply. Overexpressing or inhibiting SESN2 demonstrated that cell proliferation, casein expression, and activation of the mTORC1 pathway were all controlled by SESN2 expression. Furthermore, the increase in cell proliferation, casein expression, and activation of the mTORC1 pathway in response to AA supply was inhibited by overexpressing SESN2, and those effects were reversed by inhibiting SESN2. These results indicate that SESN2 is an important inhibitor of mTORC1 in CMEC blocking AA-mediated cell proliferation and casein synthesis.
氨基酸（AA）是调节奶牛乳腺上皮细胞（CMEC）增殖和酪蛋白合成的关键营养素之一，但这种调节的机制尚不清楚。本研究评估了 SESN2 对 AA 介导的 CMEC 细胞增殖和酪蛋白合成的影响。在 AA 饥饿 12 小时后，将 CMEC 分别在不含任何 AA（AA-）、仅含必需 AA（EAA+）或所有 AA（AA+）的条件下培养。结果发现，随着 EAA 或 AA 供应的增加，细胞增殖、酪蛋白表达和雷帕霉素靶蛋白复合物 1（mTORC1）通路的激活增加；但 SESN2 的表达减少。过表达或抑制 SESN2 表明，细胞增殖、酪蛋白表达和 mTORC1 通路的激活均受 SESN2 表达的控制。此外，过表达 SESN2 抑制了 AA 供应引起的细胞增殖、酪蛋白表达和 mTORC1 通路的激活，而抑制 SESN2 则逆转了这些效应。这些结果表明，SESN2 是 CMEC 中 mTORC1 的重要抑制剂，可阻断 AA 介导的细胞增殖和酪蛋白合成。
