Denervation-induced oxidative stress and autophagy signaling in muscle

O'Leary, Michael F. N.; Hood, David A.

doi:10.4161/auto.5.2.7391

Cited by 67 publications

(62 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As expected from previous studies,23, 44, 45, 46 the ubiquitin–proteasome and the lysosomal–autophagy pathways were activated in TIB muscle 3 days after denervation. Our results are in agreement with previous findings showing that an inhibition of the ubiquitin–proteasome system reduces muscle atrophy in a model of denervation in rats 47.…”

Section: Discussionsupporting

confidence: 88%

Urolithin B, a newly identified regulator of skeletal muscle mass

Rodriguez

Pierre

Naslain

et al. 2017

J cachexia sarcopenia muscle

View full text Add to dashboard Cite

BackgroundThe control of muscle size is an essential feature of health. Indeed, skeletal muscle atrophy leads to reduced strength, poor quality of life, and metabolic disturbances. Consequently, strategies aiming to attenuate muscle wasting and to promote muscle growth during various (pathological) physiological states like sarcopenia, immobilization, malnutrition, or cachexia are needed to address this extensive health issue. In this study, we tested the effects of urolithin B, an ellagitannin‐derived metabolite, on skeletal muscle growth.MethodsC2C12 myotubes were treated with 15 μM of urolithin B for 24 h. For in vivo experiments, mice were implanted with mini‐osmotic pumps delivering continuously 10 μg/day of urolithin B during 28 days. Muscle atrophy was studied in mice with a sciatic nerve denervation receiving urolithin B by the same way.ResultsOur experiments reveal that urolithin B enhances the growth and differentiation of C2C12 myotubes by increasing protein synthesis and repressing the ubiquitin–proteasome pathway. Genetic and pharmacological arguments support an implication of the androgen receptor. Signalling analyses suggest a crosstalk between the androgen receptor and the mTORC1 pathway, possibly via AMPK. In vivo experiments confirm that urolithin B induces muscle hypertrophy in mice and reduces muscle atrophy after the sciatic nerve section.ConclusionsThis study highlights the potential usefulness of urolithin B for the treatment of muscle mass loss associated with various (pathological) physiological states.

show abstract

Section: Discussionsupporting

confidence: 88%

Urolithin B, a newly identified regulator of skeletal muscle mass

Rodriguez

Pierre

Naslain

et al. 2017

J cachexia sarcopenia muscle

View full text Add to dashboard Cite

show abstract

“…Consistently, mice lacking either factor are resistant to neurogenic muscle atrophy [4]. Another catabolic pathway activated in skeletal muscle following denervation is autophagy [5,6]. Damaged or dysfunctional intracellular components are polyubiquitinated and included into double-membrane structures, the autophagosomes, to be degraded by autophagy.…”

Section: Introductionmentioning

confidence: 86%

HDAC4 preserves skeletal muscle structure following long-term denervation by mediating distinct cellular responses

et al. 2018

View full text Add to dashboard Cite

Background: Denervation triggers numerous molecular responses in skeletal muscle, including the activation of catabolic pathways and oxidative stress, leading to progressive muscle atrophy. Histone deacetylase 4 (HDAC4) mediates skeletal muscle response to denervation, suggesting the use of HDAC inhibitors as a therapeutic approach to neurogenic muscle atrophy. However, the effects of HDAC4 inhibition in skeletal muscle in response to long-term denervation have not been described yet. Methods: To further study HDAC4 functions in response to denervation, we analyzed mutant mice in which HDAC4 is specifically deleted in skeletal muscle. Results: After an initial phase of resistance to neurogenic muscle atrophy, skeletal muscle with a deletion of HDAC4 lost structural integrity after 4 weeks of denervation. Deletion of HDAC4 impaired the activation of the ubiquitin-proteasome system, delayed the autophagic response, and dampened the OS response in skeletal muscle. Inhibition of the ubiquitinproteasome system or the autophagic response, if on the one hand, conferred resistance to neurogenic muscle atrophy; on the other hand, induced loss of muscle integrity and inflammation in mice lacking HDAC4 in skeletal muscle. Moreover, treatment with the antioxidant drug Trolox prevented loss of muscle integrity and inflammation in in mice lacking HDAC4 in skeletal muscle, despite the resistance to neurogenic muscle atrophy. Conclusions: These results reveal new functions of HDAC4 in mediating skeletal muscle response to denervation and lead us to propose the combined use of HDAC inhibitors and antioxidant drugs to treat neurogenic muscle atrophy.

show abstract

“…In particular, the decline in mitochondrial content per gram of muscle, a major influence on muscular endurance capacity, must be a result of processes, which are independent of apoptotic signaling, such as autophagy. Although there have been reports that markers of autophagy are increased in denervated muscle (15,17,23,24,32,43) many questions still exist with regard to the functional role that this pathway has during muscle atrophy. Therefore, the main purpose of this study was to investigate whether the extent of the denervation-induced increase in autophagy was upregulated in animals with an attenuated apoptotic pathway in the absence of Bax and Bak.…”

Section: Discussionmentioning

confidence: 99%

“…Autophagy signaling is initiated in response to a multitude of factors including nutrient deprivation (12,13,25,37) or oxidative stress (6,18,24,31). Initiation of autophagy involves the activation of the unc-51 like kinase (ULK1)/ATG1 complex, which has been shown to be conserved in skeletal muscle (30), and the Beclin1/vacuole protein sorting/PI3K complex, respectively.…”

mentioning

confidence: 99%

Denervation-induced mitochondrial dysfunction and autophagy in skeletal muscle of apoptosis-deficient animals

O'Leary

Vainshtein

Carter

et al. 2012

American Journal of Physiology-Cell Physiology

Self Cite

View full text Add to dashboard Cite

-Skeletal muscle undergoes remarkable adaptations in response to chronic decreases in contractile activity, such as a loss of muscle mass, decreases in both mitochondrial content and function, as well as the activation of apoptosis. Although these adaptations are well known, questions remain regarding the signaling pathways that mediated these changes. Autophagy is an organelle turnover pathway that could contribute to these adaptations. The purpose of this study was to determine whether denervation-induced muscle disuse would result in the activation of autophagy gene expression in both wild-type (WT) and Bax/Bak double knockout (DKO) animals, which display an attenuated apoptotic response. Denervation caused a reduction in muscle mass for WT and DKO animals; however, there was a 40% attenuation in muscle atrophy in DKO animals. Mitochondrial state 3 respiration was significantly reduced, and reactive oxygen species production was increased by two-to threefold in both WT and DKO animals. Apoptotic markers, including cytosolic AIF and DNA fragmentation, were elevated in WT, but not in DKO animals following denervation. Autophagy proteins including LC3II, ULK1, ATG7, p62, and Beclin1 were increased similarly following denervation for both WT and DKO. Interestingly, denervation markedly increased the localization of LC3II to subsarcolemmal mitochondria, and this was more pronounced in the DKO animals. Thus denervation-induced muscle disuse activates both apoptotic and autophagic signaling pathways in muscle, and autophagic protein expression does not exhibit a compensatory increase in the presence of attenuated apoptosis. However, the absence of Bax and Bak may represent a potential signal to trigger mitophagy in muscle.reactive oxygen species; muscle atrophy; mitochondria; mitophagy MACROAUTOPHAGY (henceforth referred to as autophagy) is a highly conserved lysosomal-dependent degradation pathway that coordinates and oversees the digestion of organelles, proteins, and intracellular pathogens (4, 34, 42). More than 30 AuTophaGy-related (ATG) regulatory genes products have been identified that are known to facilitate the engulfment of cytoplasmic material into double-membraned vesicles called autophagosomes (4, 42), and to assist in their degradation through fusion with lysosomes (10, 21). As a consequence, autophagy plays a prominent housekeeping role, which maintains homeostasis by selectively eliminating cellular debris. Moreover, although the activity of the autophagic pathway can be increased in response to stress stimuli, the importance of maintaining adequate levels of autophagy for cellular health and function is best demonstrated in several disease conditions, such as Parkinson's and Pompe's disease (27, 41), which are attributable, at least in part, to mutations in either ATG proteins or other autophagy-related genes.Currently there is great interest in determining the meaningful purposes that autophagy has in regulating cellular health, and in more fully understanding the factors that direct selective for...

show abstract

Denervation-induced oxidative stress and autophagy signaling in muscle

Cited by 67 publications

References 14 publications

Urolithin B, a newly identified regulator of skeletal muscle mass

Urolithin B, a newly identified regulator of skeletal muscle mass

HDAC4 preserves skeletal muscle structure following long-term denervation by mediating distinct cellular responses

Denervation-induced mitochondrial dysfunction and autophagy in skeletal muscle of apoptosis-deficient animals

Contact Info

Product

Resources

About