Faculty Opinions recommendation of Little change in markers of protein breakdown and oxidative stress in humans in immobilization-induced skeletal muscle atrophy.

Although hyperhomocysteinemia (HHcy) occurs because of the deficiency in cystathionine-β-synthase (CBS) causing skeletal muscle dysfunction, it is still unclear whether this effect is mediated through oxidative stress, endoplasmic reticulum (ER) stress, or both. Nevertheless, there is no treatment option available to improve HHcy-mediated muscle injury. Hydrogen sulfide (H2S) is an antioxidant compound, and patients with CBS mutation do not produce H2S. In this study, we hypothesized that H2S mitigates HHcy-induced redox imbalance/ER stress during skeletal muscle atrophy via JNK phosphorylation. We used CBS+/−mice to study HHcy-mediated muscle atrophy, and treated them with sodium hydrogen sulfide (NaHS; an H2S donor). Proteins and mRNAs were examined by Western blots and quantitative PCR. Proinflammatory cytokines were also measured. Muscle mass and strength were studied via fatigue susceptibility test. Our data revealed that HHcy was detrimental to skeletal mass, particularly gastrocnemius and quadriceps muscle weight. We noticed that oxidative stress was reversed by NaHS in homocysteine (Hcy)-treated C2C12 cells. Interestingly, ER stress markers (GRP78, ATF6, pIRE1α, and pJNK) were elevated in vivo and in vitro, and NaHS mitigated these effects. Additionally, we observed that JNK phosphorylation was upregulated in C2C12 after Hcy treatment, but NaHS could not reduce this effect. Furthermore, inflammatory cytokines IL-6 and TNF-α were higher in plasma from CBS as compared with wild-type mice. FOXO1-mediated Atrogin-1 and MuRF-1 upregulation were attenuated by NaHS. Functional studies revealed that NaHS administration improved muscle fatigability in CBS+/−mice. In conclusion, our work provides evidence that NaHS is beneficial in mitigating HHcy-mediated skeletal injury incited by oxidative/ER stress responses.

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Skeletal Muscle Atrophy Was Alleviated by Salidroside Through Suppressing Oxidative Stress and Inflammation During Denervation

Frontiers in Pharmacology ◽

10.3389/fphar.2019.00997 ◽

2019 ◽

Vol 10 ◽

Cited By ~ 6

Author(s):

Ziwei Huang ◽

Qingqing Fang ◽

Wenjing Ma ◽

Qiuyu Zhang ◽

Jiaying Qiu ◽

...

Keyword(s):

Oxidative Stress ◽

Skeletal Muscle ◽

Muscle Atrophy ◽

Skeletal Muscle Atrophy

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Mitochondrial-targeted antioxidants protect skeletal muscle against immobilization-induced muscle atrophy

Journal of Applied Physiology ◽

10.1152/japplphysiol.00591.2011 ◽

2011 ◽

Vol 111 (5) ◽

pp. 1459-1466 ◽

Cited By ~ 127

Author(s):

Kisuk Min ◽

Ashley J. Smuder ◽

Oh-sung Kwon ◽

Andreas N. Kavazis ◽

Hazel H. Szeto ◽

...

Keyword(s):

Oxidative Stress ◽

Skeletal Muscle ◽

Muscle Atrophy ◽

Muscle Fibers ◽

Skeletal Muscle Atrophy ◽

Ros Production ◽

Oxygen Species ◽

Mitochondrial Ros ◽

Protease Activation ◽

Limb Immobilization

Prolonged periods of muscular inactivity (e.g., limb immobilization) result in skeletal muscle atrophy. Although it is established that reactive oxygen species (ROS) play a role in inactivity-induced skeletal muscle atrophy, the cellular pathway(s) responsible for inactivity-induced ROS production remain(s) unclear. To investigate this important issue, we tested the hypothesis that elevated mitochondrial ROS production contributes to immobilization-induced increases in oxidative stress, protease activation, and myofiber atrophy in skeletal muscle. Cause-and-effect was determined by administration of a novel mitochondrial-targeted antioxidant (SS-31) to prevent immobilization-induced mitochondrial ROS production in skeletal muscle fibers. Compared with ambulatory controls, 14 days of muscle immobilization resulted in significant muscle atrophy, along with increased mitochondrial ROS production, muscle oxidative damage, and protease activation. Importantly, treatment with a mitochondrial-targeted antioxidant attenuated the inactivity-induced increase in mitochondrial ROS production and prevented oxidative stress, protease activation, and myofiber atrophy. These results support the hypothesis that redox disturbances contribute to immobilization-induced skeletal muscle atrophy and that mitochondria are an important source of ROS production in muscle fibers during prolonged periods of inactivity.

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Edward F. Adolph Distinguished Lecture. Skeletal muscle atrophy: Multiple pathways leading to a common outcome

Journal of Applied Physiology ◽

10.1152/japplphysiol.00381.2020 ◽

2020 ◽

Vol 129 (2) ◽

pp. 272-282 ◽

Cited By ~ 3

Author(s):

Sue C. Bodine

Keyword(s):

Skeletal Muscle ◽

Signaling Pathways ◽

Muscle Mass ◽

Muscle Atrophy ◽

Skeletal Muscle Mass ◽

Single Gene ◽

Skeletal Muscle Atrophy ◽

Protein Breakdown ◽

E3 Ligases ◽

The Past

Skeletal muscle atrophy continues to be a serious consequence of many diseases and conditions for which there is no treatment. Our understanding of the mechanisms regulating skeletal muscle mass has improved considerably over the past two decades. For many years it was known that skeletal muscle atrophy resulted from an imbalance between protein synthesis and protein breakdown, with the net balance shifting toward protein breakdown. However, the molecular and cellular mechanisms underlying the increased breakdown of myofibrils was unknown. Over the past two decades, numerous reports have identified novel genes and signaling pathways that are upregulated and activated in response to stimuli such as disuse, inflammation, metabolic stress, starvation and others that induce muscle atrophy. This review summarizes the discovery efforts performed in the identification of several pathways involved in the regulation of skeletal muscle mass: the mammalian target of rapamycin (mTORC1) and the ubiquitin proteasome pathway and the E3 ligases, MuRF1 and MAFbx. While muscle atrophy is a common outcome of many diseases, it is doubtful that a single gene or pathway initiates or mediates the breakdown of myofibrils. Interestingly, however, is the observation that upregulation of the E3 ligases, MuRF1 and MAFbx, is a common feature of many divergent atrophy conditions. The challenge for the field of muscle biology is to understand how all of the various molecules, transcription factors, and signaling pathways interact to produce muscle atrophy and to identify the critical factors for intervention.

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Dynamics of Toll-like receptors signaling in skeletal muscle atrophy

Current Medicinal Chemistry ◽

10.2174/0929867328666210202113734 ◽

2021 ◽

Vol 28 ◽

Author(s):

Aarti Yadav ◽

Anil Dahuja ◽

Rajesh Dabur

Keyword(s):

Skeletal Muscle ◽

Muscle Atrophy ◽

Inflammatory Cytokine ◽

Muscle Growth ◽

Skeletal Muscle Atrophy ◽

Muscle Loss ◽

Protein Catabolism ◽

Tlr Signaling ◽

Recent Advancement ◽

And Oxidative Stress

: Skeletal muscle atrophy has been characterizedas a state of uncontrolled inflammation and oxidative stress that escalates the protein catabolism. Recent advancement supportsthat impinging signaling molecules in the muscle fibers controlled throughtoll-like receptors (TLR). Activated TLR signalingpathways have been identified as inhibitors of muscle mass and provoke the settings for muscle atrophy. Among them, mainly TLR2 and TLR4 manifest their presence to exacerbate the release of the pro-inflammatory cytokine to deform the synchronized muscle programming. The present review enlightens the TLR signaling mediated muscle loss and their interplay betweeninflammationand skeletal muscle growth.

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