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Methionine Protects Mammary Cells against Oxidative Stress through Producing S-Adenosylmethionine to Maintain mTORC1 Signaling Activity
- Source :
- Oxidative Medicine and Cellular Longevity, Vol 2021 (2021), Oxidative Medicine and Cellular Longevity
- Publication Year :
- 2021
- Publisher :
- Hindawi Limited, 2021.
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Aging
S-Adenosylmethionine
Article Subject
mTORC1
Mechanistic Target of Rapamycin Complex 1
medicine.disease_cause
Biochemistry
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Methionine
medicine
Animals
Humans
QH573-671
Chemistry
Kinase
Cell Biology
General Medicine
Methylation
ULK1
Cell biology
Oxidative Stress
030104 developmental biology
Phosphorylation
Female
biological phenomena, cell phenomena, and immunity
Cytology
Transmethylation
030217 neurology & neurosurgery
Oxidative stress
Research Article
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 19420994 and 19420900
- Volume :
- 2021
- Database :
- OpenAIRE
- Journal :
- Oxidative Medicine and Cellular Longevity
- Accession number :
- edsair.doi.dedup.....3750532062308aedfb2f1ce7fa2ed196