Regulatory effects of the L-lysine metabolites, L-2-aminoadipic acid and L-pipecolic acid, on protein turnover in C2C12 myotubes

Sato, Tomonori; Ito, Yoshiaki; Nagasawa, Takashi

doi:10.1080/09168451.2016.1210499

Cited by 17 publications

(10 citation statements)

References 35 publications

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“…Supplementation of lysine in rats could reduce the upregulated autophagy activity of skeletal muscle caused by a low-protein diet and activate the Akt/mTOR signaling pathways [ 24 ]. As a metabolite of lysine, pipecolic acid also could stimulate the rates of protein synthesis, contributing to the effect of lysine on protein turn over in skeletal muscle [ 25 ]. We found that serum pipecolic acid was positively associated with muscle mass and muscle strength, but negatively associated with age.…”

Section: Discussionmentioning

confidence: 99%

A joint analysis of metabolomic profiles associated with muscle mass and strength in Caucasian women

Zhao

Shen

et al. 2018

Aging

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Both loss of muscle mass and strength are important sarcopenia-related traits. In this study, we investigated both specific and shared serum metabolites associated with these two traits in 136 Caucasian women using a liquid chromatography-mass spectrometry method. A joint analysis of multivariate traits was used to examine the associations of individual metabolites with muscle mass measured by the body mass index-adjusted appendicular lean mass (ALM/BMI) and muscle strength measured by hand grip strength (HGS). After adjusting for multiple testing, nine metabolites including two amino acids (aspartic acid and glutamic acid) and an amino acid derive (pipecolic acid), one peptide (phenylalanyl-threonine), one carbohydrate (methyl beta-D-glucopyranoside), and four lipids (12S-HETRE, arachidonic acid, 12S-HETE, and glycerophosphocholine) were significant in the joint analysis. Of them, the two amino acids (aspartic acid and glutamic acid) and two lipids (12S-HETRE and 12S-HETE) were associated with both ALM/BMI and HGS, and the other five were only associated with ALM/BMI. The pathway analysis showed the amino acid metabolism pathways (aspartic acid and glutamic acid) might play important roles in the regulation of muscle mass and strength. In conclusion, our study identified novel metabolites associated with sarcopenia-related traits, suggesting novel metabolic pathways for muscle regulation.

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Section: Discussionmentioning

confidence: 99%

A joint analysis of metabolomic profiles associated with muscle mass and strength in Caucasian women

Zhao

Shen

et al. 2018

Aging

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“…α-Aminoadipic acid is a lysine metabolite which decreases fasting glucose concentrations and enhances insulin sensitivity in animals in vivo ( 71 , 72 ). α-Aminoadipic acid suppresses protein degradation and autophagy in vitro, with concomitant upregulation of the Akt/mTOR signaling pathway ( 73 ). This evidence is of interest given the elevation of this metabolite in protein-fed conditions compared with the fasted state, potentially suggesting a mitigation of protein degradation in these nutritional groups.…”

Section: Discussionmentioning

confidence: 99%

Divergent serum metabolomic, skeletal muscle signaling, transcriptomic, and performance adaptations to fasted versus whey protein-fed sprint interval training

Aird

Farquharson

Bermingham

et al. 2021

American Journal of Physiology-Endocrinology and Metabolism

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Sprint interval training (SIT) is a time efficient alternative to endurance exercise, conferring beneficial skeletal muscle metabolic adaptations. Current literature has investigated the nutritional regulation of acute and chronic exercise-induced metabolic adaptations in muscle following endurance exercise, principally comparing the impact of training in fasted and carbohydrate-fed (CHO) conditions. Alternative strategies such as exercising in low CHO, protein-fed conditions remain poorly characterised, specifically pertaining to adaptations associated with SIT. Thus, this study aimed to compare the metabolic and performance adaptations to acute and short term SIT in the fasted state with pre-exercise hydrolysed (WPH) or concentrate (WPC) whey protein supplementation. In healthy males, pre-exercise protein ingestion did not alter exercise-induced increases in PGC-1α, PDK4, SIRT1, and PPAR-δ mRNA expression following acute SIT. However, supplementation of WPC and WPH beneficially altered acute exercise-induced SIRT4 and CD36 mRNA expression, respectively. Pre-exercise protein ingestion attenuated acute exercise-induced increases in muscle pan-acetylation, and PARP1 protein content compared with fasted SIT. Acute serum metabolomic differences confirmed greater pre-exercise amino acid delivery in protein-fed compared with fasted conditions. Following 3 weeks of SIT, training-induced increases in mitochondrial enzymatic activity and exercise performance were similar across nutritional groups. Interestingly, resting muscle acetylation status was favourably regulated in WPH conditions following training. Such findings suggest pre-exercise WPC and WPH ingestion positively influences metabolic adaptations to SIT compared to fasted training, resulting in either similar or enhanced performance adaptations. Future studies investigating nutritional modulation of metabolic adaptations to exercise are warranted to build upon these novel findings.

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“…It is generally well tolerated, and skin-related complaints, nausea, and dizziness are the most common patient-reported side effects [40]. LAA, a selective astrocytic toxin, has been demonstrated to exert some regulatory effects on tibia fracture [41], myotubes [42], and retina [43], thus contributing to the fracture-induced nociceptive, cell autophagy in myotubes, and retinal vascular responses. It has not yet been clinically applied due to its unusual astroglial toxin, which may trigger locomotor network damage.…”

Section: Mediators Of Inflammationmentioning

confidence: 99%

Phosphorylation at Ser 727 Increases STAT3 Interaction with PKCε Regulating Neuron–Glia Crosstalk via IL-6-Mediated Hyperalgesia In Vivo and In Vitro

Zhou

Han

et al. 2022

Mediators of Inflammation

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Background and Aim. Interleukin-6 (IL-6) modulates neurons–glia crosstalk and subsequently triggers hyperalgesia. This study is aimed at investigating whether the interaction between protein kinase C epsilon (PKCε) and signal transducer and activator of transcription 3 (STAT3) mediated IL-6-induced hyperalgesia and neurocyte activation. Methods. A rat hyperalgesia model was induced using an intraplantar injection of Freund’s complete adjuvant (FCA) or an intrathecal injection of IL-6. Mechanical allodynia was evaluated using von Frey filament tests after intrathecal injections of T-5224 (c-Fos/AP-1 inhibitor), minocycline (Mino, a specific microglia inhibitor), L-2-aminoadipic acid (LAA, an astroglial toxin), PKCε inhibitor peptide, APTSTAT3-9R (STAT3 inhibitor), or anti-IL-6 antibody. The c-Fos, GFAP, Iba-1, PKCε, STAT3, pSTAT3Tyr705 and pSTAT3Ser727, and IL-6 expression at the spinal cord level was assessed by Western blot analysis. The interactive effects of PKCε and STAT3 were determined using immunofluorescence staining and immunoprecipitation in vivo and in vitro. Interleukin-6 promoter activity was examined using luciferase assays. Results. T-5224, Mino, and LAA attenuated FCA- or IL-6-mediated inflammatory pain, with a decrease in c-Fos, GFAP, Iba-1, PKCε, and IL-6 expression. PKCε inhibitor peptide and APTSTAT3-9R reversed FCA-induced nociceptive behavior, while decreasing pSTAT3Ser727, IL-6, c-Fos, GFAP, and Iba-1 expression and PKCε and STAT3 coexpression. Interleukin-6 promoter activity increased in the presence of PKCε and STAT3. The interaction with PKCε increased on phosphorylating STAT3 at Ser727 but not at Tyr705. Conclusion. STAT3 phosphorylation at Ser 727 and the interaction with PKCε contribute to hyperalgesia via the IL-6-mediated signaling pathway, thus regulating neuron–glia crosstalk during inflammatory pain.

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Regulatory effects of the L-lysine metabolites, L-2-aminoadipic acid and L-pipecolic acid, on protein turnover in C2C12 myotubes

Cited by 17 publications

References 35 publications

A joint analysis of metabolomic profiles associated with muscle mass and strength in Caucasian women

A joint analysis of metabolomic profiles associated with muscle mass and strength in Caucasian women

Divergent serum metabolomic, skeletal muscle signaling, transcriptomic, and performance adaptations to fasted versus whey protein-fed sprint interval training

Phosphorylation at Ser 727 Increases STAT3 Interaction with PKCε Regulating Neuron–Glia Crosstalk via IL-6-Mediated Hyperalgesia In Vivo and In Vitro

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