Abstract
Exposure to cigarette smoke (CS) and cigarette smoking have been shown to promote catabolism of skeletal muscle. Previous studies and recent findings from our laboratory have demonstrated the involvement of the ubiquitin proteasome system and the muscle-specific E3 ubiquitin ligases MAFbx/atrogin-1 and MuRF1 in CS induced skeletal muscle catabolism. The essential amino acid leucine is a known anticatabolic agent that improves skeletal muscle metabolism in various atrophic conditions. To examine the protective effect of leucine and proteasome inhibition in CS induced muscle catabolism, C2 myotubes, from an in vitro skeletal muscle cell line, were exposed to CS in the presence or absence of leucine and a proteasome inhibitor, MG132. Diameter of myotubes, levels of the main contractile proteins – myosin heavy chain and actin, expression of MAFbx/atrogin-1 and MuRF1 were studied by microscopy, Western blotting, and qPCR. Leucine pretreatment prevented the CS-induced reduction in diameter of myotubes and degradation of myosin heavy chain by suppressing the upregulation of MAFbx/atrogin-1 and MuRF1. MG132 also attenuated the CS-induced decrease in diameter of myotubes and degradation of myosin heavy chain. Our findings demonstrate that supplementation with the essential amino acid leucine and inhibition of the proteasome may protect skeletal muscle from CS induced catabolism.
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References
Baptista, I. L., Leal, M. L., Artioli, G. G., Aoki, M. S., Fiamoncini, J., Turri, A. O., Curi, R., Miyabara, E. H., & Moriscot, A. S. (2010). Leucine attenuates skeletal muscle wasting via inhibition of ubiquitin ligases. Muscle & Nerve, 41, 800–808.
Castillo, E. M., Goodman-Gruen, D., Kritz-Silverstein, D., Morton, D. J., Wingard, D. L., & Barrett-Connor, E. (2003). Sarcopenia in elderly men and women: The Rancho Bernardo study. American Journal of Preventive Medicine, 25, 226–231.
Foletta, V. C., White, L. J., Larsen, A. E., Léger, B., & Russell, A. P. (2011). The role and regulation of MAFbx/atrogin-1 and MuRF1 in skeletal muscle atrophy. Pflugers Archiv: European Journal of Physiology, 461, 325–335.
Herningtyas, E. H., Okimura, Y., Handayaningsih, A. E., Yamamoto, D., Maki, T., Iida, K., Takahashi, Y., Kaji, H., & Chihara, K. (2008). Branched-chain amino acids and arginine suppress MAFbx/atrogin-1 mRNA expression via mTOR pathway in C2C12 cell line. Biochimica et Biophysica Acta, 1780, 1115–1120.
Kisselev, A. F., & Goldberg, A. L. (2001). Proteasome inhibitors: From research tools to drug candidates. Chemistry & Biology, 8, 739–758.
Lee, J. S., Auyeung, T. W., Kwok, T., Lau, E. M., Leung, P. C., & Woo, J. (2007). Associated factors and health impact of sarcopenia in older Chinese men and women: A cross-sectional study. Gerontology, 53, 404–410.
Montes de Oca, M., Loeb, E., Torres, S. H., De Sanctis, J., Hernández, N., & Tálamo, C. (2008). Peripheral muscle alterations in non-COPD smokers. Chest, 133, 13–18.
Nicastro, H., Artioli, G. G., Costa Ados, S., Solis, M. Y., da Luz, C. R., Blachier, F., & Lancha, A. H., Jr. (2011). An overview of the therapeutic effects of leucine supplementation on skeletal muscle under atrophic conditions. Amino Acids, 40, 287–300.
Petersen, A. M., Magkos, F., Atherton, P., Selby, A., Smith, K., Rennie, M. J., Pedersen, B. K., & Mittendorfer, B. (2007). Smoking impairs muscle protein synthesis and increases the expression of myostatin and MAFbx in muscle. American Journal of Physiology. Endocrinology and Metabolism, 293, E843–E848.
Rom, O., Kaisari, S., Aizenbud, D., & Reznick, A. Z. (2012). Sarcopenia and smoking: A possible cellular model of cigarette smoke effects on muscle protein breakdown. Annals of the New York Academy of Sciences, 1259, 47–53.
Romero-Calvo, I., Ocón, B., Martínez-Moya, P., Suárez, M. D., Zarzuelo, A., Martínez-Augustin, O., & de Medina, F. S. (2010). Reversible Ponceau staining as a loading control alternative to actin in Western blots. Analytical Biochemistry, 401, 318–320.
Szulc, P., Duboeuf, F., Marchand, F., & Delmas, P. D. (2004). Hormonal and lifestyle determinants of appendicular skeletal muscle mass in men: The MINOS study. The American Journal of Clinical Nutrition, 80, 496–503.
Tang, K., Wagner, P. D., & Breen, E. C. (2010). TNF-alpha-mediated reduction in PGC-1alpha may impair skeletal muscle function after cigarette smoke exposure. Journal of Cellular Physiology, 222, 320–327.
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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Rom, O., Kaisari, S., Aizenbud, D., Reznick, A.Z. (2013). Essential Amino Acid Leucine and Proteasome Inhibitor MG132 Attenuate Cigarette Smoke Induced Catabolism in C2 Myotubes. In: Pokorski, M. (eds) Neurobiology of Respiration. Advances in Experimental Medicine and Biology, vol 788. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6627-3_4
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DOI: https://doi.org/10.1007/978-94-007-6627-3_4
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