Serine is required for the maintenance of redox balance and proliferation in the intestine under oxidative stress

Abstract

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.

Serine Metabolism Tunes Immune Responses To Promote Oreochromis niloticus Survival upon Edwardsiella tarda Infection

“…The metabolism of serine involves one-carbon metabolism. The role of serine on cancer cell and T-cell proliferation is well recognized to provide substrates for the synthesis of nucleotides, NADPH, and glutathione ( 41 , 42 ). It was recently shown that serine supports lipopolysaccharide-induced IL-1β production in macrophages ( 43 ).…”

Serine Deficiency Exacerbates Inflammation and Oxidative Stress via Microbiota-Gut-Brain Axis in D-Galactose-Induced Aging Mice

“…Serine is a nutritionally nonessential amino acid, but it is a major substrate for the synthesis of glutathione. Recent studies demonstrated that dietary supplementation with serine showed strong anti-inflammatory and antioxidative abilities in certain mouse models [7][8][9][10]. Moreover, serine exerted beneficial effects on microbiota composition and alleviated inflammatory responses in a dextran sulfate sodium-induced colitis model in mice [11].…”

Effect of dietary serine supplementation on performance, egg quality, serum indices, and ileal mucosal immunity in laying hens fed a low crude protein diet

“…Little attention has been paid to the influence of dietary Ser supplementation or its deficiency on serum biochemistry or features of the immune system of laying hens, although its anti-inflammatory and anticancer effects are well documented in vitro or in vivo ( Stiuso et al., 2016 ; Newman and Maddocks, 2017 ; He et al., 2020 ). Serum biochemical indices can partly reflect the metabolism and health status of the organism.…”

“…As the major carbon donors of one-carbon metabolism, Ser helps coordinate synthesis of nucleotide, S-adenosyl-methionine, NADPH, and glutathione ( Yang and Vousden, 2016 ). It has been confirmed that dietary Ser supplementation can prevent against oxidative stress because of its role in glutathione synthesis ( Zhou et al., 2017 ; He et al., 2020 ). Ma et al.…”