Ca<sup>2+</sup>-Calcineurin-NFAT pathway mediates the effect of thymol on oxidative metabolism and fiber-type switch in skeletal muscle

Luo, Pei; Wang, Lina; Luo, Lv; Wang, Leshan; Yang, Kelin; Shu, Gang; Zhu, Xiaotong; Gao, Ping; Jiang, Qingyan

doi:10.1039/c8fo02248h

Cited by 19 publications

(5 citation statements)

References 34 publications

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“…To better understand the pathway through which EA affects myofibre transition, we examined several potential signalling pathways, including p38 MAPK, PGC‐1α, PPAR‐δ and calcineurin‐NFAT (Luo et al, 2019; Montaigne et al, 2021; Xue et al, 2021), observing that EA significantly inhibited the phosphorylation of p38 MAPK, but had minimal effect on other signalling pathways (Figure 6a,b). An increase in DUSP1 at both the protein (Figure 6c) and gene ( p = 0.0228, ST36 vs. EA Con, Figure 6d) levels after EA treatment was also observed.…”

Section: Resultsmentioning

confidence: 99%

Effect of ST36 electroacupuncture on the switch of skeletal muscle fibres in mice with sciatic nerve dissociation

Wang,

Yao,

Xiong

et al. 2023

Eur J of Neuroscience

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Skeletal muscle is striated muscle that moves autonomously and is innervated by peripheral nerves. Peripheral nerve injury is very common in clinical treatment. However, the commonly used treatment methods often focus on the regeneration of the injured nerve but overlook the pathological changes in the injured skeletal muscle. Acupuncture, as the main treatment for denervated skeletal muscle atrophy, is used extensively in clinical practice. In the present study, a mouse model of lower limb sciatic nerve detachment was constructed and treated with electroacupuncture Stomach 36 to observe the atrophy of lower limb skeletal muscle and changes in skeletal muscle fibre types before and after electroacupuncture Stomach 36 treatment. Mice with skeletal muscle denervation showed a decrease in the proportion of IIa muscle fibres and an increase in the proportion of IIb muscle fibres, after electroacupuncture Stomach 36. The changes were reversed by specific activators of p38 MAPK, which increased IIa myofibre ratio. The results suggest that electroacupuncture Stomach 36 can reverse the change of muscle fibre type from IIb to IIa after denervation of skeletal muscle by inhibiting p38 MAPK. The results provide an important theoretical basis for the treatment of clinical peripheral nerve injury diseases with electroacupuncture, in addition to novel insights that could facilitate the study of pathological changes of denervated skeletal muscle.

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Section: Resultsmentioning

confidence: 99%

Effect of ST36 electroacupuncture on the switch of skeletal muscle fibres in mice with sciatic nerve dissociation

Wang,

Yao,

Xiong

et al. 2023

Eur J of Neuroscience

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“…Additionally, an increase in NFATc1 protein expression was induced by alternating the slow muscle fibre type (Schulz & Yutzey, 2004). Furthermore, increased calcineurin protein expression via increased nerve activity was induced by increased NFATc1 protein expression (Baldwin et al, 2013;Luo et al, 2019). Therefore, R30 supplementation may attenuate the HU-related slow-to-fast fibre type shift possibly via R30-induced activation of the calcineurin-NFAT signalling pathway, independent of the protein expression level of PGC-1α.…”

Section: Discussionmentioning

confidence: 99%

“…the typology of whole muscle fibres from slow-to fast-twitch fibres following disuse. Moreover, it has been suggested that activating the nervous system induces fibre type shifts via the calcineurin-nuclear factor of activated T-cells (NFAT) pathway, which is another regulator of fibre type shift (Luo et al, 2019). Certain lactic acid bacterial strains stimulate the autonomic nervous system via the central nervous system, and each strain has distinct effects (Horii et al, 2014;Yamano et al, 2006).…”

Section: New Findingsmentioning

confidence: 99%

Protective effects of Enterococcus faecium strain R30 supplementation on decreased muscle endurance under disuse in rats

Tanaka

Ikeji

Nakanishi

et al. 2021

Experimental Physiology

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Enterococcus faecium strain R30 (R30), a new lactic acid bacterial strain for supplementation, was hypothesized to attenuate shifts in the typology of whole muscle fibres from slow-to fast-twitch fibres in atrophied skeletal muscles. We further postulated that the prevention of slow-to-fast fibre shifts would suppress the decreased muscle endurance associated with atrophy. To evaluate the protective effects of R30, we analysed slow-to-fast fibre shifts and disuse-associated reduced muscle endurance. R30 was administered to rats with an acclimation period of 7 days before hindlimb unloading (HU) for 2 weeks. The composition ratio of the fibre type and the expression levels of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), calcineurin and nuclear factor of activated T-cells (NFAT) were measured.Muscle endurance was evaluated at the end of the 2-week HU period in an in situ environment. R30 supplementation suppressed the slow-to-fast fibre switch and decreased the HU-induced expression of PGC-1α proteins and the deactivation of the calcineurin-NFAT pathway. Furthermore, R30 prevented a decrease in HU-associated muscle endurance in calf muscles. These results indicate that R30 supplementation may attenuate the shifts in the typology of whole muscle fibres from slow-to fasttwitch fibres via the upregulation of PGC-1α and the activation of the calcineurin-NFAT signalling pathway, thereby ameliorating the decrease in muscle endurance associated with disuse.

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“…Furthermore, the activation of NFAT molecule follows the activation of Ca 2+ /calmodulin dependent phosphatase, while in T cells, the level of free Ca 2+ is higher, so the activity of Ca 2+ /calmodulin dependent phosphatase increases, and NFAT can maintain the activation state in the nucleus for a long time and promote the transcription of some genes. In addition to Ca 2+ /calmodulin dependent phosphatase, there are many proteins and signaling pathways that regulate NFAT, such as T cell receptor (TCR) cross-linking ( 49 – 51 ). Moreover, the activation of Lck and ZAP70 leads to calcium mobilization in T cells, which leads to NFAT-dependent reporter gene expression ( 52 ).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of the Expression, Relationship to Immune Infiltration and Prognosis of TIM-1 in Cancer

Kong

Niu

et al. 2020

Front. Oncol.

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TIM-1 is a critical gene that regulates T-helper cell development. However, little research has revealed the distribution, prognosis, and immune infiltration of TIM-1 in cancers. TCGA, GEO, Oncomine, TIMER, Kaplan-Meier, PrognoScan, GEPIA, TISIDB, and HPA databases were used to analyze TIM-1 in cancers. High TIM-1 expression was observed in bladder, cholangio, head and neck, colorectal, gastric, kidney, liver, lung adenocarcinoma, skin, uterine corpus endometrial, and pancreatic cancers compared to the normal tissues, and immunofluorescence shows that TIM-1 is mainly localized in vesicles. Simultaneously, high TIM-1 expression was closely related with poorer overall survival in gastric, lung adenocarcinoma, and poorer disease-specific survival in gastric cancer in the TCGA cohort, and was validated in the GEO cohort. Moreover, high expression of TIM-1, correlated with clinical relevance of gastric cancer and lung adenocarcinoma, was associated with tumor-infiltrating lymphocytes in lung adenocarcinoma and gastric cancer. Finally, immunohistochemistry showed TIM-1 expression was higher in lung adenocarcinoma and gastric cancer compared to the normal tissues. In summary, we applied integrated bioinformatics approaches to suggest that TIM-1 can be used as a prognostic biomarker in gastric and lung adenocarcinoma, which might provide a novel direction to explore the pathogenesis of gastric and lung adenocarcinoma.

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Ca²⁺-Calcineurin-NFAT pathway mediates the effect of thymol on oxidative metabolism and fiber-type switch in skeletal muscle

Abstract: Thymol is a major component of thyme, and it has been reported that thymol administration reduces body weight, plasma insulin and blood glucose in type-2 diabetes.

Cited by 19 publications

References 34 publications

Effect of ST36 electroacupuncture on the switch of skeletal muscle fibres in mice with sciatic nerve dissociation

Effect of ST36 electroacupuncture on the switch of skeletal muscle fibres in mice with sciatic nerve dissociation

Protective effects of Enterococcus faecium strain R30 supplementation on decreased muscle endurance under disuse in rats

Comprehensive Analysis of the Expression, Relationship to Immune Infiltration and Prognosis of TIM-1 in Cancer

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Ca2+-Calcineurin-NFAT pathway mediates the effect of thymol on oxidative metabolism and fiber-type switch in skeletal muscle

Abstract: Thymol is a major component of thyme, and it has been reported that thymol administration reduces body weight, plasma insulin and blood glucose in type-2 diabetes.

Cited by 19 publications

References 34 publications

Effect of ST36 electroacupuncture on the switch of skeletal muscle fibres in mice with sciatic nerve dissociation

Effect of ST36 electroacupuncture on the switch of skeletal muscle fibres in mice with sciatic nerve dissociation

Protective effects of Enterococcus faecium strain R30 supplementation on decreased muscle endurance under disuse in rats

Comprehensive Analysis of the Expression, Relationship to Immune Infiltration and Prognosis of TIM-1 in Cancer

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Product

Resources

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Ca²⁺-Calcineurin-NFAT pathway mediates the effect of thymol on oxidative metabolism and fiber-type switch in skeletal muscle