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Celastrol attenuates oxidative stress in the skeletal muscle of diabetic rats by regulating the AMPK-PGC1α-SIRT3 signaling pathway
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 t...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4829141/ https://www.ncbi.nlm.nih.gov/pubmed/27049825 http://dx.doi.org/10.3892/ijmm.2016.2549 |
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author | GUAN, YUE CUI, ZI-JIAN SUN, BEI HAN, LI-PING LI, CHUN-JUN CHEN, LI-MING |
author_facet | GUAN, YUE CUI, ZI-JIAN SUN, BEI HAN, LI-PING LI, CHUN-JUN CHEN, LI-MING |
author_sort | GUAN, YUE |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4829141 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-48291412016-04-13 Celastrol attenuates oxidative stress in the skeletal muscle of diabetic rats by regulating the AMPK-PGC1α-SIRT3 signaling pathway GUAN, YUE CUI, ZI-JIAN SUN, BEI HAN, LI-PING LI, CHUN-JUN CHEN, LI-MING Int J Mol Med Articles 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. D.A. Spandidos 2016-05 2016-04-05 /pmc/articles/PMC4829141/ /pubmed/27049825 http://dx.doi.org/10.3892/ijmm.2016.2549 Text en Copyright: © Guan et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles GUAN, YUE CUI, ZI-JIAN SUN, BEI HAN, LI-PING LI, CHUN-JUN CHEN, LI-MING Celastrol attenuates oxidative stress in the skeletal muscle of diabetic rats by regulating the AMPK-PGC1α-SIRT3 signaling pathway |
title | Celastrol attenuates oxidative stress in the skeletal muscle of diabetic rats by regulating the AMPK-PGC1α-SIRT3 signaling pathway |
title_full | Celastrol attenuates oxidative stress in the skeletal muscle of diabetic rats by regulating the AMPK-PGC1α-SIRT3 signaling pathway |
title_fullStr | Celastrol attenuates oxidative stress in the skeletal muscle of diabetic rats by regulating the AMPK-PGC1α-SIRT3 signaling pathway |
title_full_unstemmed | Celastrol attenuates oxidative stress in the skeletal muscle of diabetic rats by regulating the AMPK-PGC1α-SIRT3 signaling pathway |
title_short | Celastrol attenuates oxidative stress in the skeletal muscle of diabetic rats by regulating the AMPK-PGC1α-SIRT3 signaling pathway |
title_sort | celastrol attenuates oxidative stress in the skeletal muscle of diabetic rats by regulating the ampk-pgc1α-sirt3 signaling pathway |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4829141/ https://www.ncbi.nlm.nih.gov/pubmed/27049825 http://dx.doi.org/10.3892/ijmm.2016.2549 |
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