Serine is required for the maintenance of redox balance and proliferation in the intestine under oxidative stress.
Serine has critical roles in maintaining cell growth and redox balance in cancer cells. However, the role of exogenous serine played in oxidative response and proliferation in normal mammalian intestine need to be further elucidated. We used a mouse model and intestinal porcine epithelial cells (IPEC-J2) to reveal that exogenous serine deficiency did not lead to redox imbalance and inhibition of proliferation in the intestine. However, serine deficiency exacerbated oxidative stress, mitochondrial dysfunction, apoptosis, and inhibition of proliferation in IPEC-J2 cells challenged by hydrogen peroxide, while serine supplementation rescued redox imbalance and those proliferation defects. Importantly, serine supplementation restored the glutathione content and decreased the accumulation of reactive oxygen species, while no such effects were observed when glutathione synthesis was inhibited. Additionally, serine supplementation increased nuclear nrf2 expression in IPEC-J2 cells. These results suggested that serine alleviates oxidative stress through supporting glutathione synthesis and activating nrf2 signaling. We further found that serine supplementation activated the mTOR pathway, while inhibition of mTOR diminished the effects of serine on promoting proliferation, suggesting critical roles of the mTOR pathway in this context. Taken together, our study underlines the importance of serine in the maintenance of redox status and proliferation in the intestine and reveals a novel potential mechanism that mediates these effects.
['He|Liuqin|L|', 'Long|Jing|J|', 'Zhou|Xihong|X|', 'Liu|Yonghui|Y|', 'Li|Tiejun|T|', 'Wu|Xin|X|']
D000818:Animals D002453:Cell Cycle D002460:Cell Line D049109:Cell Proliferation D002470:Cell Survival D047209:Eosinophil Peroxidase D005978:Glutathione D007413:Intestinal Mucosa D007770:L-Lactate Dehydrogenase D051379:Mice D008810:Mice, Inbred C57BL D051267:NF-E2-Related Factor 2 D010084:Oxidation-Reduction D018384:Oxidative Stress D009195:Peroxidase D012694:Serine D015398:Signal Transduction D013552:Swine D058570:TOR Serine-Threonine Kinases
cell growth apoptosis glutathione reactive oxygen species