Calycosin inhibited autophagy and oxidative stress in chronic kidney disease skeletal muscle atrophy by regulating AMPK/SKP2/CARM1 signalling pathway

Hu, Rong; Wang, Mingqing; Liu, Lingyu; You, Hyun Ju; Wu, Xiaohui; Liu, Yang‐yang; Wang, Yan‐jing; Lu, Lu; Xiao, Wei; Wei, Lianbo

doi:10.1111/jcmm.15514

Cited by 38 publications

(33 citation statements)

References 59 publications

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“…Notably, GCs induction of muscle atrophy-associated protein breakdown appears to involve effects on transcription factor production, specifically of forkhead box (Fox) O1, FoxO3a ( 12 ) and GSK3β ( 13 ), that trigger ubiquitin proteasome system-dependent proteolysis of muscle proteins and subsequent autophagy ( 14 ). Meanwhile, studies of muscle atrophy induced by denervation have identified increased mitochondrial fission and resulting fragmentation as key signals responsible for triggering the AMP-activated kinase-forkhead box O3 (AMPK-FoxO3) signaling pathway ( 15 , 16 ). Mitochondria are organelles that provide energy to cells.…”

Section: Introductionmentioning

confidence: 99%

20(s)‑ginseonside‑Rg3 modulation of AMPK/FoxO3 signaling to attenuate mitochondrial dysfunction in a dexamethasone‑injured C2C12 myotube‑based model of skeletal atrophy in vitro

et al. 2021

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Muscle atrophy, a side effect from administration of the anti-inflammatory medication dexamethasone (DEX), is preventable by concomitant administration of the major monomeric constituent of Panax ginseng C.A. Meyer, 20(S)-ginsenoside Rg3 (S-Rg3). Putative S-Rg3-associated prevention of DEX-induced muscle atrophy may involve S-Rg3 mitigation of DEX-induced mitochondrial dysfunction. In the present study, MTT assays revealed enhanced cell viability following S-Rg3 treatment of DEX-injured C2C12 myotubes. Subsequent PCR and western blotting results demonstrated S-Rg3-induced reduction of expression of muscle atrophy F-box protein (atrogin-1) and muscle RING-finger protein-1, proteins previously linked to muscle atrophy. Additionally, S-Rg3 treatment of DEX-injured myotubes led to aggregation of Rg3 monomers in cells and dose-dependent increases in cellular mitochondrial basal respiratory oxygen consumption rate and intracellular ATP levels compared with their levels in untreated DEX-injured myotubes. In addition, S-Rg3 treatment significantly reversed DEX-induced reductions of expression of key mitochondrial respiratory electron transport chain subunits of protein complexes II, III and V in DEX-injured myotube cells. Furthermore, S-Rg3 alleviation of mitochondrial dysfunction associated with DEX-induced injury of C2C12 myotubes was linked to S-Rg3-associated decreases in both forkhead box O3 (FoxO3) protein expression and phosphorylation of AMP-activated protein kinase (AMPK). Collectively, these results implicate S-Rg3 modulation of signaling within the AMPK-FoxO3 pathway as a putative mechanism underlying S-Rg3 alleviation of DEX-induced muscle atrophy.

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Section: Introductionmentioning

confidence: 99%

20(s)‑ginseonside‑Rg3 modulation of AMPK/FoxO3 signaling to attenuate mitochondrial dysfunction in a dexamethasone‑injured C2C12 myotube‑based model of skeletal atrophy in vitro

et al. 2021

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“…Although low muscle mass, low muscle strength and low physical performance are closely related, there is not yet an agreement on which operational criteria to apply when diagnosing muscle atrophy in CKD patients ( Sabatino et al, 2021 ). Muscle mass and physical performance were determined as direct indicators of muscle atrophy in CKD model rats based on our previous studies ( Wang et al, 2019 ; Hu et al, 2020 ; Liu et al, 2021 ). The PF-treated group was confirmed by an increase in body weight, muscle weight and muscle fiber CSA.…”

Section: Discussionmentioning

confidence: 99%

“…The nephrectomized group rats underwent a 5/6 nephrectomy surgical resection of the upper and lower thirds of the left kidney and were subjected to right nephrectomy after 1 week. The Sham group rats were treated as described previously ( Wang et al, 2019 ; Hu et al, 2020 ; Liu et al, 2021 ). Rats were observed postprocedure for 1–2 h, and their wound healing, movements, mental states and body weights were monitored weekly.…”

Section: Methodsmentioning

confidence: 99%

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Paeoniflorin Ameliorates Skeletal Muscle Atrophy in Chronic Kidney Disease via AMPK/SIRT1/PGC-1α-Mediated Oxidative Stress and Mitochondrial Dysfunction

Huang

et al. 2022

Front. Pharmacol.

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Skeletal muscle atrophy is a common and serious complication of chronic kidney disease (CKD). Oxidative stress and mitochondrial dysfunction are involved in the pathogenesis of muscle atrophy. The aim of this study was to explore the effects and mechanisms of paeoniflorin on CKD skeletal muscle atrophy. We demonstrated that paeoniflorin significantly improved renal function, calcium/phosphorus disorders, nutrition index and skeletal muscle atrophy in the 5/6 nephrectomized model rats. Paeoniflorin ameliorated the expression of proteins associated with muscle atrophy and muscle differentiation, including muscle atrophy F-box (MAFbx/atrogin-1), muscle RING finger 1 (MuRF1), MyoD and myogenin (MyoG). In addition, paeoniflorin modulated redox homeostasis by increasing antioxidant activity and suppressing excessive accumulation of reactive oxygen species (ROS). Paeoniflorin alleviated mitochondrial dysfunction by increasing the activities of electron transport chain complexes and mitochondrial membrane potential. Furthermore, paeoniflorin also regulates mitochondrial dynamics. Importantly, paeoniflorin upregulated the expression of silent information regulator 1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and phosphorylation of AMP-activated protein kinase (AMPK). Similar results were observed in C2C12 myoblasts treated with TNF-α and paeoniflorin. Notably, these beneficial effects of paeoniflorin on muscle atrophy were abolished by inhibiting AMPK and SIRT1 and knocking down PGC-1α. Taken together, this study showed for the first time that paeoniflorin has great therapeutic potential for CKD skeletal muscle atrophy through AMPK/SIRT1/PGC-1α-mediated oxidative stress and mitochondrial dysfunction.

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“…Unfortunately, the molecular mechanisms linking pathogenetic factors in kidney brosis are complicated and incompletely understood 5,6 . It is most likely a combination of oxidative stress [7][8][9][10] , in ammation [11][12][13] , epithelial to mesenchymal transition, apoptosis 14 , and extracellular matrix deposition 15 . Thus, studies aimed at exploring attractive therapeutic targets and developing corresponding approaches for the treatment of CKD are urgently needed.…”

Section: Introductionmentioning

confidence: 99%

Design and discovery of a highly potent ultralong-acting GLP-1 and glucagon co-agonist for attenuating renal fibrosis by modulating mitochondrial function

Jiang

Zhao²,

Dong³

et al. 2022

Preprint

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GLP-1 receptor (GLP-1R) and glucagon receptor (GCGR) are critical for the maintenance of glucose and energy homeostasis, but their roles in chronic kidney disease (CKD) are still unknown. Herein we found that the expression of GLP-1R and GCGR was lower in kidney from patients with CKD than in control individuals and was correlated with disease severity. RNA-seq analysis showed that adeno-associated viral vector serotype 9-GLP-1R or GCGR small hairpin RNA (AAV9-GLP-1R or GCGR shRNA) treatment in db/db mice exhibited more advanced diabetic nephropathy than wild-type mice. We also found that GLP-1R mainly expressed in glomeruli and GCGR expressed in both glomeruli and tubuli renales. Based on the importance of GLP-1R and GCGR in CKD, we design and report a new monomeric peptide, 1907-B, with agonism at the GLP-1R and GCGR that have more prolonged half-time than long-acting semaglutide in cynomolgus rats or monkeys (~2-3 fold) and exhibit better therapeutic contribution to CKD than best-in-class monoagonists, semaglutide or glucagon in db/db mice and unilateral ureter obstruction (UUO) mice. Various loss-of-function models, including selective pharmacological blockade and genetic knockdown, confirmed that the effects of 1907-B on improving glucose control and ameliorating the diabetic nephropathy in db/db mice were mediated through GLP-1 and glucagon signaling, whereas its action on inhibiting renal fibrosis in UUO mice was predominantly mediated through glucagon signaling. Mechanistically, 1907-B activated downstream cAMP-PKA pathway to promote mitochondrial biogenesis and bioenergetics, as well as to attenuate renal oxidative stress under chronic hyperglycemia via stimulating GLP-1R and GCGR simultaneously. Furthermore, 1907-B had crucial protection roles against inflammation via NFκB pathway and renal fibrosis via TGF-β-SMAD pathway. Thus 1907-B, via direct kidney (GCGR) and part-glomerulus (GLP-1R) effects, exerts multifactorial improvement in renal injuries and is a more effective and promising therapeutic option for the treatment of CKD.

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Calycosin inhibited autophagy and oxidative stress in chronic kidney disease skeletal muscle atrophy by regulating AMPK/SKP2/CARM1 signalling pathway

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 38 publications

References 59 publications

20(s)‑ginseonside‑Rg3 modulation of AMPK/FoxO3 signaling to attenuate mitochondrial dysfunction in a dexamethasone‑injured C2C12 myotube‑based model of skeletal atrophy in vitro

20(s)‑ginseonside‑Rg3 modulation of AMPK/FoxO3 signaling to attenuate mitochondrial dysfunction in a dexamethasone‑injured C2C12 myotube‑based model of skeletal atrophy in vitro

Paeoniflorin Ameliorates Skeletal Muscle Atrophy in Chronic Kidney Disease via AMPK/SIRT1/PGC-1α-Mediated Oxidative Stress and Mitochondrial Dysfunction

Design and discovery of a highly potent ultralong-acting GLP-1 and glucagon co-agonist for attenuating renal fibrosis by modulating mitochondrial function

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