Skeletal Muscle Is a Primary Target of SOD1G93A-Mediated Toxicity

被引：419

作者：

Dobrowolny, Gabriella

Aucello, Michela

Rizzuto, Emanuele

Beccafico, Sara ^{[2
]}

Mammucari, Cristina ^{[3
]}

Bonconpagni, Simona ^{[2
]}

Belia, Silvia ^{[3
]}

Wannenes, Francesca ^{[4
,5
]}

Nicoletti, Carmine

Del Prete, Zaccaria ^{[6
]}

Rosenthal, Nadia ^{[7
]}

Molinaro, Mario

Protasi, Feliciano ^{[2
]}

Fano, Giorgio ^{[2
]}

Sandri, Marco ^{[8
,9
]}

Musaro, Antonio ^{[1
,10
]}

机构：

[1] Univ Roma La Sapienza, Dept Histol & Med Embryol, CE BEMM, Inst Pasteur Cenci Bolognetti, I-00161 Rome, Italy

[2] Univ G DAnnunzio, IIM, CeSI Ctr Sci Invecchiamento, I-66100 Chieti, Italy

[3] Univ Perugia, Lab Interuniv Miol, I-06100 Perugia, Italy

[4] IUSM, Dept Sci Human Movement & Sport, I-00100 Rome, Italy

[5] CNR, INMM, I-00100 Rome, Italy

[6] Univ Roma La Sapienza, Dept Mech Engn, I-00184 Rome, Italy

[7] EMBL Mouse Biol Program, I-00016 Monterotondo, Italy

[8] Univ Padua, Dulbecco Telethon Inst, I-35100 Padua, Italy

[9] Venetian Inst Mol Med, I-35100 Padua, Italy

[10] Edith Cowan Univ, Perth, WA 6027, Australia

来源：

CELL METABOLISM | 2008年 / 8卷 / 05期

关键词：

D O I：

10.1016/j.cmet.2008.09.002

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：425 / 436

页数：12

共 39 条

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