FoxO3 Coordinately Activates Protein Degradation by the Autophagic/Lysosomal and Proteasomal Pathways in Atrophying Muscle Cells

Zhao, Jinghui; Brault, Jeffrey J.; Schild, Andreas; Cao, Peirang; Sandri, Marco; Schiaffino, Stefano; Lecker, Stewart H.; Goldberg, Alfred L.

doi:10.1016/j.cmet.2007.11.004

Cited by 1,281 publications

(1,334 citation statements)

References 53 publications

Supporting

Mentioning

1,249

Contrasting

Unclassified

Order By: Relevance

“…The Akt/FoxO3 pathway has been involved in both autophagic and proteasomal degradation pathways in skeletal muscle 42. FoxO3 activation drives the expression of key autophagic genes such as LC3, Bnip‐3, and Gabarap1 43. However, we have previously reported that adjuvant‐induced arthritis does not change Akt or FoxO3 phosphorylation in gastrocnemius,44 suggesting no involvement of this mechanism in activating autophagy or atrogene up‐regulation in gastrocnemius.…”

Section: Discussionmentioning

confidence: 77%

The melanocortin receptor type 3 agonistd-Trp(8)-γMSH decreases inflammation and muscle wasting in arthritic rats

Gómez-SanMiguel

Martín

Nieto-Bona

et al. 2015

Journal of Cachexia, Sarcopenia and Muscle

View full text Add to dashboard Cite

BackgroundChronic inflammatory diseases induce cachexia that increases mortality and morbidity of the illness. Adjuvant‐induced arthritis is an experimental model of rheumatoid arthritis that is associated with body weight loss and muscle wasting. Alpha‐melanocyte stimulating hormone has an anti‐inflammatory effect in arthritic rats and decreases muscle wasting. The aim of this work was to elucidate whether the anti‐cachectic action of alpha‐melanocyte stimulating hormone is mediated by the melanocortin receptor type 3 pathway.MethodsArthritis was induced in male Wistar rats by intradermal injection of Freund's adjuvant, and 6 days afterwards, arthritic rats were injected with the selective melanocortin receptor type 3 agonist d‐Trp(8)‐gammaMSH ( d‐Trp(8)‐γMSH) 500 µg/kg subcutaneously. or saline twice a day, for 10 days.Results d‐Trp(8)‐γMSH decreased the external signs of inflammation and body weight loss, but it was not able to modify the anorexigenic effect of arthritis or the increase in hypothalamic cyclooxygenase‐2 (COX‐2) expression. In contrast, d‐Trp(8)‐γMSH prevented arthritis‐induced increase in hypothalamic IL‐1β and serum corticosterone levels and the decrease in serum IGF‐I levels. d‐Trp(8)‐γMSH treatment also prevented arthritis‐induced NF‐kB(p65) phosphorylation and tumour necrosis factor‐α mRNA increase in the gastrocnemius. d‐Trp(8)‐γMSH administration to arthritic rats increased gastrocnemius mass, its cross‐sectional area, and mean fast fibre area. Those effects of d‐Trp(8)‐γMSH were associated with a decreased expression of atrogin‐1 and muscle ring‐finger protein‐1 in the gastrocnemius. In rats treated with saline, arthritis increased the expression of autophagy marker genes LC3b, Bnip‐3, and Gabarap1 as well as the conversion of LC3b I to LC3b II by lipidation in the gastrocnemius. d‐Trp(8)‐γMSH decreased gastrocnemius LC3b, Bnip‐3, and Gabarap1 mRNA expression and prevented the increase in LC3b II in arthritic rats.ConclusionThese data suggest that d‐Trp(8)‐γMSH administration prevents the effect of arthritis on corticosterone and insulin‐like growth factor‐I serum levels and decreases muscle wasting, by down‐regulating atrogenes and autophagy through modifying the NF‐kB(p65)/tumour necrosis factor‐α signalling transduction pathway.

show abstract

Section: Discussionmentioning

confidence: 77%

The melanocortin receptor type 3 agonistd-Trp(8)-γMSH decreases inflammation and muscle wasting in arthritic rats

Gómez-SanMiguel

Martín

Nieto-Bona

et al. 2015

Journal of Cachexia, Sarcopenia and Muscle

View full text Add to dashboard Cite

show abstract

“…We also analysed whether urolithin B was capable of repressing the autophagy–lysosomal pathway, which is another important proteolytic pathway in muscle regulated by mTORC1 and FoxOs as well 23, 24. No markers of autophagy that we studied were changed in the presence of urolithin B.…”

Section: Resultsmentioning

confidence: 99%

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

“…Sandri et al reported the role for lysosome activity in muscle degradation during cancer cachexia. Actually, activation of FoxO3 stimulates lysosomal proteolysis in muscle by inducing the expression of autophagy‐related genes 46. It has been recently shown that autophagy plays a relevant role even in cancer cachexia 47.…”

Section: Resultsmentioning

confidence: 99%

A multifactorial anti-cachectic approach for cancer cachexia in a rat model undergoing chemotherapy

Toledo

Penna

Oliva

et al. 2015

Journal of Cachexia, Sarcopenia and Muscle

View full text Add to dashboard Cite

BackgroundThe effectiveness of drugs aimed at counteracting cancer cachexia is generally tested in pre‐clinical rodent models, where only the tumour‐induced alterations are taken into account, excluding the co‐presence of anti‐tumour molecules that could worsen the scenario and/or interfere with the treatment.MethodsThe aim of the present investigation has been to assess the efficacy of a multifactorial treatment, including formoterol and megestrol acetate, in cachectic tumour‐bearing rats (Yoshida AH‐130, a highly cachectic tumour) undergoing chemotherapy (sorafenib).ResultsTreatment of cachectic tumour‐bearing rats with sorafenib (90 mg/kg) causes an important decrease in tumour cell content due to both reduced cell proliferation and increased apoptosis. As a consequence, animal survival significantly improves, while cachexia occurrence persists. Multi‐factorial treatment using both formoterol and megestrol acetate is highly effective in preventing muscle wasting and has more powerful effects than the single formoterol administration. In addition, both physical activity and grip strength are significantly improved as compared with the untreated tumour‐bearing animals. The effects of the multi‐factorial treatment include increased food intake (likely due to megestrol acetate) and decreased protein degradation, as shown by the reduced expression of genes associated with both proteasome and calpain proteolytic systems.ConclusionsThe combination of the two drugs proved to be a promising strategy for treating cancer cachexia in a pre‐clinical setting that better resembles the human condition, thus providing a strong rationale for the use of such combination in clinical trials involving cachectic cancer patients.

show abstract

FoxO3 Coordinately Activates Protein Degradation by the Autophagic/Lysosomal and Proteasomal Pathways in Atrophying Muscle Cells

Cited by 1,281 publications

References 53 publications

The melanocortin receptor type 3 agonistd-Trp(8)-γMSH decreases inflammation and muscle wasting in arthritic rats

The melanocortin receptor type 3 agonistd-Trp(8)-γMSH decreases inflammation and muscle wasting in arthritic rats

Urolithin B, a newly identified regulator of skeletal muscle mass

A multifactorial anti-cachectic approach for cancer cachexia in a rat model undergoing chemotherapy

Contact Info

Product

Resources

About