Vikas Dutt1, Vikram Saini2, Prachi Gupta1, Nirmaljeet Kaur1, Manju Bala1, Ravindra Gujar3, Anita Grewal4, Sanjeev Gupta1, Anita Dua1, Ashwani Mittal5. 1. Skeletal Muscle Laboratory, University College, Kurukshetra University, Kurukshetra, Haryana 136119, India. 2. Department of Microbiology, Center for Free Radical Biology, University of Alabama, Birmingham 35205, USA; Department of Biotechnology, All India Institute of Medical Sciences, New Delhi 110029, India. 3. CSIR-Institute of Microbial Technology, Sector 39A, Chandigarh 160036, India. 4. Biotechnology Department, UIET, Kurukshetra University, Kurukshetra, Haryana 136119, India. 5. Skeletal Muscle Laboratory, University College, Kurukshetra University, Kurukshetra, Haryana 136119, India. Electronic address: mittala@kuk.ac.in.
Abstract
BACKGROUND: Elevated levels of inflammatory molecules are key players in muscle wasting/atrophy leading to human morbidity. TNFα is a well-known pro-inflammatory cytokine implicated in the pathogenesis of muscle wasting under diverse clinical settings. S-allyl cysteine (SAC), an active component of garlic (Allium sativum), has established anti-oxidant and anti-inflammatory effects in various cell types. However, the impact of SAC on skeletal muscle pathology remains unexplored. Owing to the known anti-inflammatory properties of SAC, we investigated whether pre-treatment with SAC has a protective role in TNFα-induced atrophy in cultured myotubes. METHODS AND RESULTS: C2C12 myotubes were treated with TNFα (100ng/ml) in the presence or absence of SAC (0.01mM). TNFα treatment induced atrophy in myotubes by up-regulating various proteolytic systems i.e. cathepsin L, calpain, ubiquitin-proteasome E3-ligases (MuRF1/atrogin1), caspase 3 and autophagy (Beclin1/LC3B). TNFα also induced the activation of NFκB by stimulating the degradation of IκBα (inhibitor of NFκB), in myotubes. The alterations in proteolytic systems likely contribute to the degradation of muscle-specific proteins and reduce the myotube length, diameter and fusion index. The SAC supplementation significantly impedes TNFα-induced protein loss and protects myotube morphology by suppressing protein catabolic systems and endogenous level of inflammatory molecules namely TNFα, IL-6, IL-1β, TNF-like weak inducer of apoptosis (TWEAK), fibroblast growth factor-inducible 14 (Fn14) and Nox. CONCLUSION AND GENERAL SIGNIFICANCE: Our findings reveal anti-atrophic role for SAC, as it prevents alterations in protein metabolism and protects myotubes by regulating the level of inflammatory molecules and multiple proteolytic systems responsible for muscle atrophy.
BACKGROUND: Elevated levels of inflammatory molecules are key players in muscle wasting/atrophy leading to human morbidity. TNFα is a well-known pro-inflammatory cytokine implicated in the pathogenesis of muscle wasting under diverse clinical settings. S-allyl cysteine (SAC), an active component of garlic (Allium sativum), has established anti-oxidant and anti-inflammatory effects in various cell types. However, the impact of SAC on skeletal muscle pathology remains unexplored. Owing to the known anti-inflammatory properties of SAC, we investigated whether pre-treatment with SAC has a protective role in TNFα-induced atrophy in cultured myotubes. METHODS AND RESULTS: C2C12 myotubes were treated with TNFα (100ng/ml) in the presence or absence of SAC (0.01mM). TNFα treatment induced atrophy in myotubes by up-regulating various proteolytic systems i.e. cathepsin L, calpain, ubiquitin-proteasome E3-ligases (MuRF1/atrogin1), caspase 3 and autophagy (Beclin1/LC3B). TNFα also induced the activation of NFκB by stimulating the degradation of IκBα (inhibitor of NFκB), in myotubes. The alterations in proteolytic systems likely contribute to the degradation of muscle-specific proteins and reduce the myotube length, diameter and fusion index. The SAC supplementation significantly impedes TNFα-induced protein loss and protects myotube morphology by suppressing protein catabolic systems and endogenous level of inflammatory molecules namely TNFα, IL-6, IL-1β, TNF-like weak inducer of apoptosis (TWEAK), fibroblast growth factor-inducible 14 (Fn14) and Nox. CONCLUSION AND GENERAL SIGNIFICANCE: Our findings reveal anti-atrophic role for SAC, as it prevents alterations in protein metabolism and protects myotubes by regulating the level of inflammatory molecules and multiple proteolytic systems responsible for muscle atrophy.
Authors: Alexey M Petrov; Maria N Shalagina; Vladimir A Protopopov; Valeriy G Sergeev; Sergey V Ovechkin; Natalia G Ovchinina; Alexey V Sekunov; Andrey L Zefirov; Guzalia F Zakirjanova; Irina G Bryndina Journal: Int J Mol Sci Date: 2019-09-30 Impact factor: 5.923
Authors: Yann S Gallot; Kyle R Bohnert; Alex R Straughn; Guangyan Xiong; Sajedah M Hindi; Ashok Kumar Journal: FASEB J Date: 2018-09-11 Impact factor: 5.834