S-allyl cysteine regulates the TNFα-induced muscle wasting by suppressing proteolysis and regulating the inflammatory molecules in skeletal muscle myotubes.

S-allyl cysteine regulates the TNFα-induced muscle wasting by suppressing proteolysis and regulating the inflammatory molecules in skeletal muscle myotubes.

Biochim Biophys Acta. 2017 Dec 27;:

Authors: Dutt V, Saini V, Gupta P, Kaur N, Bala M, Gujar R, Grewal A, Gupta S, Dua A, Mittal A

Abstract
BACKGROUND: Elevated levels of inflammatory molecules are the 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 investigate 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 (0.01 mM). 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. These alterations in proteolytic systems likely contribute in the degradation of muscle-specific proteins (MHCf) and reduce the myotube length, diameter and fusion index. The SAC supplementation significantly impedes TNFα-induced protein loss and protects the 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 of SAC as it prevents alterations in protein metabolism and protects the myotubes by regulating the level of inflammatory molecules and multiple proteolytic systems responsible for muscle atrophy.

PMID: 29288771 [PubMed - as supplied by publisher]

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