The antioxidant enzyme superoxide dismutase 1 (SOD1) is a critical player of the antioxidative defense whose activity is altered in several chronic diseases, including amyotrophic lateral sclerosis. However, how oxidative insult affects muscle homeostasis remains unclear. This study addresses the role of oxidative stress on muscle homeostasis and function by the generation of a transgenic mouse model expressing a mutant SOD1 gene (SOD1(G93A)) selectively in skeletal muscle. Transgenic mice developed progressive muscle atrophy, associated with a significant reduction in muscle strength, alterations in the contractile apparatus, and mitochondrial dysfunction. The analysis of molecular pathways associated with muscle atrophy revealed that accumulation of oxidative stress served as signaling molecules to initiate autophagy, one of the major intracellular degradation mechanisms. These data demonstrate that skeletal muscle is a primary target of SOD1(G93A) -mediated toxicity and disclose the molecular mechanism whereby oxidative stress triggers muscle atrophy.

Skeletal muscle is a primary target of SOD1G93A-mediated toxicity / Dobrowolny, Gabriella; Aucello, M; Rizzuto, Emanuele; Beccafico, S; Mammucari, C; Bonconpagni, S; Belia, S; Wannenes, F; Nicoletti, Carmine; DEL PRETE, Zaccaria; Rosenthal, N; Molinaro, Mario; Protasi, F; Fanò, G; Sandri, M; Musaro', Antonio. - In: CELL METABOLISM. - ISSN 1550-4131. - 8:(2008), pp. 425-436. [10.1016/j.cmet.2008.09.002]

Skeletal muscle is a primary target of SOD1G93A-mediated toxicity

DOBROWOLNY, Gabriella;RIZZUTO, EMANUELE;NICOLETTI, CARMINE;DEL PRETE, Zaccaria;MOLINARO, Mario;MUSARO', Antonio
2008

Abstract

The antioxidant enzyme superoxide dismutase 1 (SOD1) is a critical player of the antioxidative defense whose activity is altered in several chronic diseases, including amyotrophic lateral sclerosis. However, how oxidative insult affects muscle homeostasis remains unclear. This study addresses the role of oxidative stress on muscle homeostasis and function by the generation of a transgenic mouse model expressing a mutant SOD1 gene (SOD1(G93A)) selectively in skeletal muscle. Transgenic mice developed progressive muscle atrophy, associated with a significant reduction in muscle strength, alterations in the contractile apparatus, and mitochondrial dysfunction. The analysis of molecular pathways associated with muscle atrophy revealed that accumulation of oxidative stress served as signaling molecules to initiate autophagy, one of the major intracellular degradation mechanisms. These data demonstrate that skeletal muscle is a primary target of SOD1(G93A) -mediated toxicity and disclose the molecular mechanism whereby oxidative stress triggers muscle atrophy.
2008
Humdisease; molneuro
01 Pubblicazione su rivista::01a Articolo in rivista
Skeletal muscle is a primary target of SOD1G93A-mediated toxicity / Dobrowolny, Gabriella; Aucello, M; Rizzuto, Emanuele; Beccafico, S; Mammucari, C; Bonconpagni, S; Belia, S; Wannenes, F; Nicoletti, Carmine; DEL PRETE, Zaccaria; Rosenthal, N; Molinaro, Mario; Protasi, F; Fanò, G; Sandri, M; Musaro', Antonio. - In: CELL METABOLISM. - ISSN 1550-4131. - 8:(2008), pp. 425-436. [10.1016/j.cmet.2008.09.002]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/363586
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