| 저자(한글) |
Xia, Xiaojing,Che, Yanyi,Gao, Yuanyuan,Zhao, Shuang,Ao, Changjin,Yang, Hongjian,Liu, Juxiong,Liu, Guowen,Han, Wenyu,Wang, Yuping,Lei, Liancheng |
| 초록 |
During the lactation cycle of the bovine mammary gland, autophagy is induced in bovine mammary epithelial cells (BMECs) as a cellular homeostasis and survival mechanism. Interferon gamma ( $IFN-{ gamma}$ ) is an important antiproliferative and apoptogenic factor that has been shown to induce autophagy in multiple cell lines in vitro. However, it remains unclear whether $IFN-{ gamma}$ can induce autophagy and whether autophagy affects milk synthesis in BMECs. To understand whether $IFN-{ gamma}$ affects milk synthesis, we isolated and purified primary BMECs and investigated the effect of $IFN-{ gamma}$ on milk synthesis in primary BMECs in vitro. The results showed that $IFN-{ gamma}$ significantly inhibits milk synthesis and that autophagy was clearly induced in primary BMECs in vitro within 24 h. Interestingly, autophagy was observed following $IFN-{ gamma}$ treatment, and the inhibition of autophagy can improve milk protein and milk fat synthesis. Conversely, upregulation of autophagy decreased milk synthesis. Furthermore, mechanistic analysis confirmed that $IFN-{ gamma}$ mediated autophagy by depleting arginine and inhibiting the general control nonderepressible-2 kinase (GCN2)/eukaryotic initiation factor $2{ alpha}$ ( $eIF2{ alpha}$ ) signaling pathway in BMECs. Then, it was found that arginine supplementation could attenuate $IFN-{ gamma}$ -induced autophagy and recover milk synthesis to some extent. These findings may not only provide a novel measure for preventing the $IFN-{ gamma}$ -induced decrease in milk quality but also a useful therapeutic approach for $IFN-{ gamma}$ -associated breast diseases in other animals and humans. |
