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Calycosin inhibited autophagy and oxidative stress in chronic kidney disease skeletal muscle atrophy by regulating AMPK/SKP2/CARM1 signalling pathway
- Source :
- Journal of Cellular and Molecular Medicine
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- Skeletal muscle atrophy is a common and serious complication of chronic kidney disease (CKD). Oxidative stress and autophagy are the primary molecular mechanisms involved in muscle atrophy. Calycosin, a major component of Radix astragali, exerts anti‐inflammatory, anti‐oxidative stress and anti‐autophagy effects. We investigated the effects and mechanisms of calycosin on skeletal muscle atrophy in vivo and in vitro. 5/6 nephrectomy (5/6 Nx) rats were used as a model of CKD. We evaluated bodyweight and levels of serum creatinine (SCr), blood urea nitrogen (BUN) and serum albumin (Alb). H&E staining, cell apoptosis, oxidative stress biomarkers, autophagosome and LC3A/B levels were performed and evaluated in skeletal muscle of CKD rat. Calycosin treatment improved bodyweight and renal function, alleviated muscle atrophy (decreased the levels of MuRF1 and MAFbx), increased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH‐Px) activity and reduced malondialdehyde (MDA) levels in skeletal muscle of CKD rats. Importantly, calycosin reduced autophagosome formation, down‐regulated the expression of LC3A/B and ATG7 through inhibition of AMPK and FOXO3a, and increased SKP2, which resulted in decreased expression of CARM1, H3R17me2a. Similar results were observed in C2C12 cells treated with TNF‐α and calycosin. Our findings showed that calycosin inhibited oxidative stress and autophagy in CKD induced skeletal muscle atrophy and in TNF‐α‐induced C2C12 myotube atrophy, partially by regulating the AMPK/SKP2/CARM1 signalling pathway.
- Subjects :
- Male
AMPK
0301 basic medicine
Protein-Arginine N-Methyltransferases
Muscle Fibers, Skeletal
Apoptosis
AMP-Activated Protein Kinases
Kidney
medicine.disease_cause
Nephrectomy
Histones
Rats, Sprague-Dawley
Mice
chemistry.chemical_compound
0302 clinical medicine
oxidative stress
S-Phase Kinase-Associated Proteins
chemistry.chemical_classification
Chemistry
Glutathione peroxidase
Calycosin
Muscle atrophy
Muscular Atrophy
medicine.anatomical_structure
030220 oncology & carcinogenesis
Molecular Medicine
Original Article
SKP2
medicine.symptom
Signal Transduction
autophagy
medicine.medical_specialty
Down-Regulation
Arginine
Methylation
Cell Line
03 medical and health sciences
skeletal muscle atrophy
Atrophy
Internal medicine
medicine
Animals
Renal Insufficiency, Chronic
Muscle, Skeletal
Tumor Necrosis Factor-alpha
Body Weight
Autophagy
Skeletal muscle
Original Articles
Cell Biology
medicine.disease
Fibrosis
Isoflavones
CARM1
030104 developmental biology
Endocrinology
Oxidative stress
Subjects
Details
- ISSN :
- 15824934 and 15821838
- Volume :
- 24
- Database :
- OpenAIRE
- Journal :
- Journal of Cellular and Molecular Medicine
- Accession number :
- edsair.doi.dedup.....545d0f092520336f3d75380299785684