Heju Zhong, Peiqiang Yuan, Yunxia Li, Dolores Batonon-Alavo, Caroline Deschamps, Bin Feng, Xiaoling Zhang, Lianqiang Che, Yan Lin, Shengyu Xu, Jian Li, Yong Zhuo, Gang Tian, Jiayong Tang, Xuemei Jiang, Lingjie Huang, Caimei Wu, De Wu, Zhengfeng Fang

6
Jul 20, 2021
Oxidative Medicine and Cellular Longevity
DOI :
10.1155/2021/5550196
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The mechanistic target of rapamycin complex 1 (mTORC1) signaling plays pivotal roles in cell growth and diseases. However, it remains mechanistically unclear about how to maintain mTORC1 activity during mammary glands development. Here we showed that mammary glands suffered from aggravated oxidative stress as pregnancy advanced and was accompanied by an increase in H2O2 levels, while the consumption for methionine and S adenosylmethionine (SAM) rather than S adenosylhomocysteine (SAH) were promoted in vivo. Likewise, H2O2 promoted SAM synthesis and reduced SAM utilization for methylation depending on H2O2 levels and treatment time in vitro. H2O2 inhibited phosphorylation of S6 kinase Thr 389 (p S6K1 (T389)), 4E BP1 Thr 37/46 and ULK1 Ser 757, the downstream of mTORC1, in mammary epithelial cells. However, methionine and SAM were shown to activate mTORC1 under H2O2 exposed condition. Moreover, this effect was not disabled by SGI 1027 which inhibits SAM transmethylation. In conclusion, methionine appeared to protect mammary cells against oxidative stress through producing SAM to maintain mTORC1 signaling activity.
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