Eldecalcitol prevents muscle loss by suppressing PI3K/AKT/FOXOs pathway in orchiectomized mice

Zhang, Haichao; Ke, Zheng; Dong, Shuangshuang; Du, Yan; Tang, Wenjing; Chen, Minmin; Yu, Weijia; Cheng, Qun

doi:10.3389/fphar.2022.1018480

Cited by 3 publications

(2 citation statements)

References 54 publications

(62 reference statements)

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“…Multiple signaling pathways are involved in the regulation of Atrogin-1 expression. For example, the PI3K/AKT/FOXOs signaling pathway affects Atrogin-1 in muscle atrophy models through the FOXO family by recruiting Atrogin-1 promoter pairs and thus regulating its protein expression ( 28 , 29 ). In the IL-6/JAK/STAT3 signaling pathway, STAT3 phosphorylation activates CCAAT/enhancer binding protein delta, increasing Atrogin-1 expression ( 30 ).…”

Section: Discussionmentioning

confidence: 99%

ROS in diabetic atria regulate SK2 degradation by Atrogin-1 through the NF-κB signaling pathway

Xu,

Zhang,

et al. 2024

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

ROS in diabetic atria regulate SK2 degradation by Atrogin-1 through the NF-κB signaling pathway

Xu,

Zhang,

et al. 2024

Journal of Biological Chemistry

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“…Micro-computed tomography (CT) was performed as described in our previous study [ 41 ]. Femurs were fixed in 4% paraformaldehyde for 12 h and transferred to 75% ethanol at 4 °C for analyzing bone microarchitecture by micro-CT at the resolution of 8.96 μm, voltage of 50 kV, and current of 450 mA.…”

Section: Methodsmentioning

confidence: 99%

Eldecalcitol prevents muscle loss and osteoporosis in disuse muscle atrophy via NF-κB signaling in mice

Zhang,

Du,

Tang

et al. 2023

Skeletal Muscle

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We investigated the effect of eldecalcitol on disuse muscle atrophy. C57BL/6J male mice aged 6 weeks were randomly assigned to control, tail suspension (TS), and TS-eldecalcitol–treated groups and were injected intraperitoneally twice a week with either vehicle (control and TS) or eldecalcitol at 3.5 or 5 ng for 3 weeks. Grip strength and muscle weights of the gastrocnemius (GAS), tibialis anterior (TA), and soleus (SOL) were determined. Oxidative stress was evaluated by malondialdehyde, superoxide dismutase, glutathione peroxidase, and catalase. Bone microarchitecture was analyzed using microcomputed tomography. The effect of eldecalcitol on C2C12 myoblasts was analyzed by measuring myofibrillar protein MHC and the atrophy markers Atrogin-1 and MuRF-1 using immunofluorescence. The influence of eldecalcitol on NF-κB signaling pathway and vitamin D receptor (VDR) was assessed through immunofluorescence, (co)-immunoprecipitation, and VDR knockdown studies. Eldecalcitol increased grip strength (P < 0.01) and restored muscle loss in GAS, TA, and SOL (P < 0.05 to P < 0.001) induced by TS. An improvement was noted in bone mineral density and bone architecture in the eldecalcitol group. The impaired oxidative defense system was restored by eldecalcitol (P < 0.05 to P < 0.01 vs. TS). Eldecalcitol (10 nM) significantly inhibited the expression of MuRF-1 (P < 0.001) and Atrogin-1 (P < 0.01), increased the diameter of myotubes (P < 0.05), inhibited the expression of P65 and P52 components of NF-κB and P65 nuclear location, thereby inhibiting NF-κB signaling. Eldecalcitol promoted VDR binding to P65 and P52. VDR signaling is required for eldecalcitol-mediated anti-atrophy effects. In conclusion, eldecalcitol exerted its beneficial effects on disuse-induced muscle atrophy via NF-κB inhibition.

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Comparative Proteomic Analysis of Glycolytic and Oxidative Muscle in Pigs

Tan

et al. 2023

Genes

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The quality of meat is highly correlated with muscle fiber type. However, the mechanisms via which proteins regulate muscle fiber types in pigs are not entirely understood. In the current study, we have performed proteomic profiling of fast/glycolytic biceps femoris (BF) and slow/oxidative soleus (SOL) muscles and identified several candidate differential proteins among these. We performed proteomic analyses based on tandem mass tags (TMTs) and identified a total of 26,228 peptides corresponding to 2667 proteins among the BF and SOL muscle samples. Among these, we found 204 differentially expressed proteins (DEPs) between BF and SOL muscle, with 56 up-regulated and 148 down-regulated DEPs in SOL muscle samples. KEGG and GO enrichment analyses of the DEPs revealed that the DEPs are involved in some GO terms (e.g., actin cytoskeleton, myosin complex, and cytoskeletal parts) and signaling pathways (PI3K-Akt and NF-kappa B signaling pathways) that influence muscle fiber type. A regulatory network of protein–protein interaction (PPI) between these DEPs that regulates muscle fiber types was constructed, which demonstrates how three down-regulated DEPs, including PFKM, GAPDH, and PKM, interact with other proteins to potentially control the glycolytic process. This study offers a new understanding of the molecular mechanisms in glycolytic and oxidative muscles as well as a novel approach for enhancing meat quality by transforming the type of muscle fibers in pigs.

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Eldecalcitol prevents muscle loss by suppressing PI3K/AKT/FOXOs pathway in orchiectomized mice

Cited by 3 publications

References 54 publications

ROS in diabetic atria regulate SK2 degradation by Atrogin-1 through the NF-κB signaling pathway

ROS in diabetic atria regulate SK2 degradation by Atrogin-1 through the NF-κB signaling pathway

Eldecalcitol prevents muscle loss and osteoporosis in disuse muscle atrophy via NF-κB signaling in mice

Comparative Proteomic Analysis of Glycolytic and Oxidative Muscle in Pigs

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