Oxidative Stress Impairs Skeletal Muscle Repair in Diabetic Rats

Abstract

Alongside increased proteolysis, the inability to repair damaged skeletal muscle is a characteristic feature of uncontrolled diabetes. This study evaluates the role of oxidative stress in muscle-specific gene regulatory regions and myosin chain synthesis in streptozotocin (STZ)-induced diabetic and ZDF rats. In the gastrocnemius muscle of diabetic rats, prooxidant compounds were seen to increase while antioxidant levels fell. Myogenic regulatory factors-Myo, myogenin, and Jun D-were also reduced, and muscle enhancer factor (MEF)-1 DNA binding activity was impaired. Moreover, synthesis of muscle creatine kinase and both heavy and light chains of myosin were impaired, suggesting that oxidative stress triggers the cascade of events that leads to impaired muscle repair. Dehydroepiandrosterone has been reported to possess antioxidant properties. When it was administered to diabetic rats, in addition to an improved oxidative imbalance there was a recovery of myogenic factors, MEF-1 DNA binding activity, synthesis of muscle creatine kinase, and myosin light and heavy chains. Vitamin E administration to STZ-induced diabetic rats reverses oxidative imbalance and improves muscle gene transcription, reinforcing the suggestion that oxidative stress may play a role in diabetes-related impaired muscle repair. Diabetes

Myostatin Induces DNA Damage in Skeletal Muscle of Streptozotocin-induced Type 1 Diabetic Mice

“…Such an autoregulatory mechanism would help maintain increased levels of Foxa2 in STZ-treated WT mice and lower levels in Mstn Ϫ/Ϫ mice. In line with earlier findings (32,33,34), increased ROS was observed (and thus Anti-oxidant enzymes) in skeletal muscles of WT diabetic mice via TNF-␣, Nox1 (Fig. 1, A and B) and lipid peroxidation (data not shown).…”

Effect of dehydroepiandrosterone on protein and fat digestibility, body protein and muscular composition in high-fat-diet-fed old rats

“…Because of its accessibility, the gastrocnemius muscle has been previously studied to analyse the specific effects of DHEA on skeletal muscle (Hansen et al 1997;Aragno et al 2004;Campbell et al 2004). In the present study, a larger gastrocnemius size relative to total body mass was found in DHEA-treated rats compared with control ones.…”

Participação do estresse oxidativo na disfunção muscular esquelética em ratos diabéticos.

“…Pacientes com diabetes apresentam estresse oxidativo sistêmico (Bonnard et al, 2008;Ramakrishna, Jailkhani, 2008) que envolve diferentes tecidos (Maritim et al, 2003;Matkovics et al, 1997), incluindo músculo esquelético (Aragno et al, 2004;Bravard et al, 2011;Gumieniczeket al, 2001;Matkovics et al, 1997). O estresse oxidativo nestas condições pode ser induzido pelas concentrações elevadas de glicose e AGL plasmáticos (Bloch-Damti, Bashan, 2005;Brownlee, 2001;Jellinger, 2007;Kraegen, Cooney, 2008) típicas da doença.…”

“…A capacidade de ligação ao sítio MEF-1 (do inglês muscle enhancer factor-1) do DNA (uma seqüência a qual se ligam MRFs e que é fundamental para a expressão de alguns genes específicos de músculo esquelético) é reduzida em ratos diabéticos e o estresse oxidativo é um dos mediadores deste efeito (Aragno et al,2004). Portanto, outros mecanismos, além da modulação da expressão dos MRFs, também comprometem a miogênese no diabetes.…”