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Peroxynitrite Induces Degradation of Myosin Heavy Chain via p38 MAPK and Muscle-Specific E3 Ubiquitin Ligases in C2 Skeletal Myotubes

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Oxidative Stress and Cardiorespiratory Function

Part of the book series: Advances in Experimental Medicine and Biology ((NR,volume 832))

Abstract

Oxidative stress and inflammation play an important role in the catabolism of skeletal muscles. Recently, cigarette smoke (CS) was shown to stimulate muscle catabolism by activation of p38 MAPK and up-regulation of the muscle-specific E3 ubiquitin ligases (E3s) atrogin-1 and MuRF1 which are over-expressed during muscle atrophy. Peroxynitrite (ONOO), an oxidative ingredient of CS, also produced during oxidative stress and inflammation, was previously shown to induce ubiquitination and degradation of muscle proteins. To investigate the involvement of p38 MAPK and the muscle-specific E3s in ONOO-induced muscle catabolism, C2 myotubes, differentiated from a myoblast cell line, were exposed to ONOO (25 μM) in a time-dependent manner. Following exposure, degradation of myosin heavy chain (MyHC) and actin, activation of p38 MAPK, and levels of atrogin-1 and MuRF1 were studied by Western blotting. Peak phosphorylation of p38 MAPK was observed at 1 h of ONOO exposure. ONOO caused a significant increase in the levels of atrogin-1 and MuRF1. In accordance, a significant decrease in MyHC levels was observed in a time-dependent manner. These findings support previous studies in which the catabolic effects of ONOO were shown. In addition, ONOO was demonstrated to induce degradation of muscle proteins by activation of p38 MAPK and up-regulation of the muscle-specific E3s atrogin-1 and MuRF1.

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Acknowledgments

This study was supported by grants from the Rappaport Institute, the Krol Foundation of Barnegat N.J., the Myers-JDC-Brookdale Institute of Gerontology and Human Development, and ESHEL – the association for planning and development of services for the aged in Israel.

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The authors declare no conflicts of interest in relation to this article.

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Correspondence to A. Z. Reznick .

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Rom, O., Kaisari, S., Reznick, A.Z., Aizenbud, D. (2014). Peroxynitrite Induces Degradation of Myosin Heavy Chain via p38 MAPK and Muscle-Specific E3 Ubiquitin Ligases in C2 Skeletal Myotubes. In: Pokorski, M. (eds) Oxidative Stress and Cardiorespiratory Function. Advances in Experimental Medicine and Biology(), vol 832. Springer, Cham. https://doi.org/10.1007/5584_2014_9

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