Redox control of skeletal muscle atrophy

Abstract

Skeletal muscles comprise the largest organ system in the body and play an essential role in body movement, breathing, and glucose homeostasis. Skeletal muscle is also an important endocrine organ that contributes to the health of numerous body organs. Therefore, maintaining healthy skeletal muscles is important to support overall health of the body. Prolonged periods of muscle inactivity (e.g., bed rest or limb immobilization) or chronic inflammatory diseases (i.e., cancer, kidney failure, etc.) result in skeletal muscle atrophy. An excessive loss of muscle mass is associated with a poor prognosis in several diseases and significant muscle weakness impairs the quality of life. The skeletal muscle atrophy that occurs in response to inflammatory diseases or prolonged inactivity is often associated with both oxidative and nitrosative stress. In this report, we critically review the experimental evidence that provides support for a causative link between oxidants and muscle atrophy. More specifically, this review will debate the sources of oxidant production in skeletal muscle undergoing atrophy as well as provide a detailed discussion on how reactive oxygen species and reactive nitrogen species modulate the signaling pathways that regulate both protein synthesis and protein breakdown.

Reduced mitochondrial lipid oxidation leads to fat accumulation in myosteatosis

“…We also observed increased markers of ROS in injured muscles, including elevated levels of glutathionylated proteins, as well as an increase in the abundance of Prdx3 and Prdx6, which scavenge hydrogen peroxide in the mitochondria and cytoplasm, respectively (69,70). The production of ROS by dysfunctional mitochondria, as suggested by the elevation in Prdx3, likely further exacerbates the inflammatory environment within injured rotator cuff muscle fibers because elevated ROS has been linked to inhibition of protein synthesis signaling pathways, the induction of proteolytic and autophagic pathways, and fibrosis (71,72). To address the dysfunctional mitochondria, injured rotator cuff muscle fibers do appear to be activating mitophagy, as evidenced by increased levels of PINK1 and Parkin, which target depolarized mitochondria for breakdown in autophagosomes in a processe mediated by ULK1 (73).…”

Sarcolemmal loss of active nNOS (Nos1) is an oxidative stress‐dependent, early event driving disuse atrophy

“…Although a large body of evidence supports the contribution of oxidative stress to the development of disuse muscle atrophy , data showing the causal role of reactive oxygen species (ROS) are scant. Several factors, among which disruption of the intracellular antioxidant defense, due to both decreased gene expression and increased protein catabolism , and the occurrence of transient cellular antioxidant stress responses, complicate the picture . For the latter case, we detected blunted protein carbonylation in both human T8 muscle biopsies and rat U1 soleus (this study) concomitantly with the upregulation of the stress protein/chaperone Grp75 .…”

Stress Effects on Meat Quality: A Mechanistic Perspective

“…Calcium plays a crucial role in regulating intracellular biological events including gene transcription, cell differentiation, and tissue development (Tu, Levin, Hamilton, & Borodinsky, 2016). As an intracellular 2nd messenger, ROS can trigger diverse signaling transduction pathways by oxidation of pivotal molecules including kinases, redox sensitive transcription factors, cell cycle regulators, and cell membrane lipids (Powers, Morton, Ahn, & Smuder, 2016). Increasing evidence suggests that ROS production and the calcium signaling pathways are closely connected; increased calcium influx can promote relevant enzymes to generate free radicals, while ROS overproduction can also lead to the breakdown of Ca 2+ homeostasis (Görlach, Bertram, Hudecova, & Krizanova, 2015).…”