title: Celastrol attenuates oxidative stress in the skeletal muscle of diabetic rats by regulating the AMPK-PGC1α-SIRT3 signaling pathway.
abstract: Oxidative stress plays a key role in the pathogenesis of diabetic myopathy. Celastrol provides a wide range of health benefits, including antioxidant, anti-inflammatory and antitumor effects. We hypothesized that celastrol may exert an antioxidant effect in the skeletal muscle of diabetic rats. In the present study, MnSOD activity was determined by spectrophotometry. The protein levels were evaluated by western blot analysis and mRNA content was quantified by RT‑qPCR. We firstly found that the levels of AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor coactivator 1α (PGC1α), silent mating-type information regulation 2 homolog 3 (Sirt3) and manganese superoxide dismutase (MnSOD) were all decreased in the skeletal muscle of diabetic patients. Male rats with diabetes were also treated with the vehicle or with celastrol at 1, 3 and 6 mg/kg/day for 8 weeks. The administration of celastrol at 3 and 6 mg/kg attenuated the deterioration of skeletal muscle, as shown by histological analysis, decreased the malondialdehyde (MDA) level and increased the glutathione (GSH) level assayed by enzyme-linked immunosorbent assay (ELISA) method. It also enhanced the enzyme activity and increased the expression of MnSOD, and increased the AMPK phosphorylation level, as well as PGC1α and Sirt3 expression. The findings of our study suggest that the expression of AMPK, PGC1α, Sirt3 and MnSOD are decreased in the skeletal muscle of diabetic patients. Celastrol exerted antioxidant effects on skeletal muscle partly by regulating the AMPK-PGC1α-Sirt3 signaling pathway.
authors.affiliation: Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, P.R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Department of Spinal Surgery, Tianjin Union Medicine Center, Tianjin 300121, P.R. China.
authors.forename: Zi-Jian
authors.initials: ZJ
authors.lastname: Cui
authors.affiliation: Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, P.R. China.
authors.forename: Bei
authors.initials: B
authors.lastname: Sun
authors.affiliation: Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, P.R. China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Han
authors.affiliation: Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, P.R. China.
authors.forename: Chun-Jun
authors.initials: CJ
authors.lastname: Li
authors.affiliation: Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, P.R. China.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Chen
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000368:Aged; D000818:Animals; D015415:Biomarkers; D003920:Diabetes Mellitus / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D053978:Pentacyclic Triterpenes; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D056566:Sirtuin 3 / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D053978:Pentacyclic Triterpenes; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D014315:Triterpenes; D013482:Superoxide Dismutase; D055372:AMP-Activated Protein Kinases; D056566:Sirtuin 3; C050414:celastrol