L-Serine: a Naturally-Occurring Amino Acid with Therapeutic Potential

Metcalf, James S.; Dunlop, Rachael A.; Powell, James T.; Banack, Sandra Anne; Cox, Paul Alan

doi:10.1007/s12640-017-9814-x

Cited by 69 publications

(48 citation statements)

References 80 publications

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“…Research examining the impacts of dietary serine supplementation on humans and rodents showed no adverse effects [4]. Our recent studies with mice showed that serine, as a precursor of glutathione, could alleviate hepatic oxidative stress by regulating the expression of glutathionesynthesis-related genes and increasing glutathione concentration [6,7].…”

Section: Introductionmentioning

confidence: 96%

“…Serine, recently classified as a conditionally non-essential amino acid, has been suggested as playing important roles ranging from protein synthesis to cell signal transduction, the latter mostly through post-translational modification by phosphorylation [4,5]. Research examining the impacts of dietary serine supplementation on humans and rodents showed no adverse effects [4].…”

Section: Introductionmentioning

confidence: 99%

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Effects of Dietary Serine Supplementation on Intestinal Integrity, Inflammation and Oxidative Status in Early-Weaned Piglets

Zhou

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Early weaning often causes gut dysfunction. Since serine alleviates oxidative stress and inflammatory response which are accompany with early weaning, we conducted the study to explore whether serine improves intestinal function in early-weaned piglets. Methods: Twenty-eight weaned piglets (aged 21 d) were fed either a basal diet or a basal diet plus 0.2% serine. We determined the effects of dietary serine supplementation on intestinal morphology by hematoxylin and eosin staining, expression of tight junction proteins (TJPs) by immunoblotting and immunofluorescence, expression of inflammatory cytokines and apoptosis markers by RT-qPCR and the level of antioxidant enzymes with ELISA kits in early-weaned piglets. Results: Serine supplementation increased daily body weight gain while decreasing diarrhea incidence. Both the jejunum and ileum of serine-supplemented piglets showed regularly arranged villi and microvilli. Moreover, dietary serine increased TJP expression, and alleviated apoptosis, inflammation, and oxidative stress in the intestine of early-weaned piglets. Conclusion: Our findings suggest that serine has the potential for use as a feed additive to prevent gut dysfunction caused by weaning.

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Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Effects of Dietary Serine Supplementation on Intestinal Integrity, Inflammation and Oxidative Status in Early-Weaned Piglets

Zhou

Zhang

et al. 2018

Cell Physiol Biochem

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“…In addition, l -serine exerts critical functions in the mammalian central nervous system. It serves as a precursor of the neuroactive substances l -serine and glycine, and mediates neuroprotective effects ( 25 , 26 ). However, it remains unknown whether l -serine has any effects on age-related oxidative stress in the hypothalamus.…”

Section: Introductionmentioning

confidence: 99%

Long-Term l-Serine Administration Reduces Food Intake and Improves Oxidative Stress and Sirt1/NFκB Signaling in the Hypothalamus of Aging Mice

Zhou

Zhang

et al. 2018

Front. Endocrinol.

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Serine has recently been shown to reduce oxidative stress and inflammation, which, when occurring in the hypothalamus, contribute to age-related obesity. To explore whether long-term serine administration reduces oxidative stress and body weight in aging mice, various concentrations of l-serine dissolved in water were administered to 18-month-old C57BL/6J mice for 6 months. The results showed that the administration of 0.5% (w/v) l-serine significantly reduced food intake and body weight gain during the experiment. Moreover, the administration of 0.5% l-serine decreased the concentrations of leptin, malondialdehyde, interleukin-1β, and interleukin-6, while it increased those of superoxide dismutase and glutathione, in both the serum and hypothalamus. Reactive oxygen species and the activity of nicotinamide adenine dinucleotide phosphate oxidase were reduced in the hypothalamus of aging mice treated with l-serine as compared with untreated control mice. Additionally, the expression of the leptin receptor increased while the levels of neuropeptide Y and agouti-related protein decreased in mice that had been treated with 0.5% l-serine. The expression of Sirt1 and phosphorylated signal transducers and activators of transcription 3 (pSTAT3) increased, while that of phosphorylated NFκB decreased in the mice treated with 0.5% l-serine. These results indicated that long-term l-serine administration reduces body weight by decreasing orexigenic peptide expression and reduces oxidative stress and inflammation during aging in mice, possibly by modulating the Sirt1/NFκB pathway. Thus, l-serine has the potential to be used in the prevention of age-related obesity.

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“…Evidence for non-primary protein association in favor of misincorporation also exists [ 34 ]. Furthermore, despite reports that BMAA does not misincorporate into proteins in bacteria or in a rat pheochromocytoma cell line [ 34 , 69 ] it has been suggested that the lack of prokaryote misincorporation may not hold true in eukaryotes [ 75 ], although the authors cite Glover et al [ 32 ] in support of their hypothesis, despite their use of a prokaryotic expression system. In this study, human cell lines were therefore used to evaluate BMAA misincorporation using both toxicological markers and amino acid compositional analysis of purified proteins from exposed cell lines, with reference to known misincorporating amino acid analogues.…”

Section: Introductionmentioning

confidence: 99%

Investigating β-N-Methylamino-l-alanine Misincorporation in Human Cell Cultures: A Comparative Study with Known Amino Acid Analogues

Onselen

Downing

Kemp

et al. 2017

Toxins

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Misincorporation of β-N-methylamino-l-alanine (BMAA) into proteins has been proposed to be a mechanism of toxicity to explain the role of BMAA in neurodegenerative disease development. However, studies have shown that all detectable BMAA can be removed from proteins by SDS-PAGE purification and that the toxicity of l-canavanine cannot be reproduced in prokaryotes or in a rat pheochromocytoma cell line, strongly indicating that the misincorporation hypothesis of BMAA should be re-investigated. The aim of this study was therefore to determine if BMAA misincorporates into proteins in cells of human origin with subsequent misincorporation-type toxicity. Almost complete loss of viability in response to exposure to l-4-fluorophenylalanine and l-m-tyrosine was observed in all of the cell lines, corresponding to a concentration-dependent increase of the analogues in protein extracts from exposed cells. In contrast, BMAA exposure resulted in slight toxicity in one of the cell lines but the observed toxicity was not the result of misincorporation of BMAA into proteins, as no BMAA was detected in any of the SDS-PAGE purified protein extracts that were obtained from the cells following BMAA exposure. The results show that BMAA is not misincorporated into human proteins and that misincorporation is not a valid mechanism of toxicity.

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L-Serine: a Naturally-Occurring Amino Acid with Therapeutic Potential

Cited by 69 publications

References 80 publications

Effects of Dietary Serine Supplementation on Intestinal Integrity, Inflammation and Oxidative Status in Early-Weaned Piglets

Effects of Dietary Serine Supplementation on Intestinal Integrity, Inflammation and Oxidative Status in Early-Weaned Piglets

Long-Term l-Serine Administration Reduces Food Intake and Improves Oxidative Stress and Sirt1/NFκB Signaling in the Hypothalamus of Aging Mice

Investigating β-N-Methylamino-l-alanine Misincorporation in Human Cell Cultures: A Comparative Study with Known Amino Acid Analogues

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