Modulation of reactive oxygen species in skeletal muscle by myostatin is mediated through NF-κB
| Autor: | Craig McFarlane, Ravi Kambadur, Mridula Sharma, Durgalakshmi Sathiakumar, Subha Subramanian, Mônica Senna Salerno, Sandhya Sriram, Rithika Venkatesh |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
chemistry.chemical_classification
Aging Reactive oxygen species medicine.medical_specialty NADPH oxidase biology Skeletal muscle Cell Biology Myostatin Protein degradation medicine.disease_cause medicine.disease medicine.anatomical_structure Endocrinology chemistry Internal medicine Sarcopenia biology.protein medicine Myocyte Oxidative stress |
| Zdroj: | Aging Cell. 10:931-948 |
| ISSN: | 1474-9718 |
| DOI: | 10.1111/j.1474-9726.2011.00734.x |
| Popis: | Abnormal levels of reactive oxygen species (ROS) and inflammatory cytokines have been observed in the skeletal muscle during muscle wasting including sarcopenia. However, the mechanisms that signal ROS production and prolonged maintenance of ROS levels during muscle wasting are not fully understood. Here, we show that myostatin (Mstn) is a pro-oxidant and signals the generation of ROS in muscle cells. Myostatin, a transforming growth factor-β (TGF-β) family member, has been shown to play an important role in skeletal muscle wasting by increasing protein degradation. Our results here show that Mstn induces oxidative stress by producing ROS in skeletal muscle cells through tumor necrosis factor-α (TNF-α) signaling via NF-κB and NADPH oxidase. Aged Mstn null (Mstn(-/-) ) muscles, which display reduced sarcopenia, also show an increased basal antioxidant enzyme (AOE) levels and lower NF-κB levels indicating efficient scavenging of excess ROS. Additionally, our results indicate that both TNF-α and hydrogen peroxide (H(2) O(2) ) are potent inducers of Mstn and require NF-κB signaling for Mstn induction. These results demonstrate that Mstn and TNF-α are components of a feed forward loop in which Mstn triggers the generation of second messenger ROS, mediated by TNF-α and NADPH oxidase, and the elevated TNF-α in turn stimulates Mstn expression. Higher levels of Mstn in turn induce muscle wasting by activating proteasomal-mediated catabolism of intracellular proteins. Thus, we propose that inhibition of ROS induced by Mstn could lead to reduced muscle wasting during sarcopenia. |
| Databáze: | OpenAIRE |
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