Evidence for autophagy attenuation during post-mortem maturation of hypertrophied muscle in myostatin deficient mice - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement Access content directly
Conference Poster Year : 2017

Evidence for autophagy attenuation during post-mortem maturation of hypertrophied muscle in myostatin deficient mice

Barbara Vernus
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  • PersonId : 1202944
Gilles Fouret
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  • PersonId : 1019222
Lionel Tintignac
  • Function : Author
  • PersonId : 1206019
Iban Seiliez
Arnaud Chatonnet
Anne Bonnieu
Béatrice Chabi

Abstract

The conversion of skeletal muscle into meat, i.e. maturation, is a complex process where muscle undergoes different biochemical and physiological changes. In agronomic field, the study of these events is of particular interest, in order to improve the quality of the final product put on the market. If the characterization of the proteolytic mechanisms involved in skeletal muscle maturation is still ongoing, the participation of autophagy in this process is still under debate. In order to decipher the involvement of autophagy during skeletal muscle maturation, the expression and activation of keys proteins regulating this process have been followed within a 48h postmortem (PM) time frame in mice. The interaction between autophagy and myostatin, a negative regulator of skeletal muscle mass, was also analyzed during this post-mortem interval. Using 6 month-old wild-type (WT) and myostatin knocked-out (Mstn KO) mice, we measured the proteolysis of myofibrillar proteins (filamin and troponin T), as well as the activation and expression of proteins involved in autophagic pathway (AMPK, FOXO, ULK, LC3 and p62). Our results showed a progressive degradation of myofibrillar proteins over the 48h PM period. Moreover, it was more pronounced in gastrocnemius muscle of Mstn KO mice when compared to WT mice. AMPK activation was more marked in WT mice, with a maximal induction between 2 and 4h PM, suggestive of an energetic stress. Inhibition of Foxo1 phosphorylation (Thr24) was relieved in the late PM interval (8h PM) in both genotypes, indicating the activation of proteolytic pathways. Concerning autophagy, the phosphorylation profile of ULK1 (Ser757 vs Ser555) suggests an early activation (1h PM) of autophagy in Mstn KO mice. To estimate the autophagic flux, LC3 and p62 protein expression were measured after autophagy blockade with colchicine at 0h, 4h, 8h and 24h postmortem. Our results showed a higher flux in the WT mice compared to Mstn KO mice, whatever the PM time. In conclusion, our data showed that autophagy is maintained during skeletal muscle PM maturation, but to a lower extent in Mstn-deficient mice, suggesting a relationship between myostatin and autophagy.
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Dates and versions

hal-02940597 , version 1 (16-09-2020)

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  • HAL Id : hal-02940597 , version 1

Cite

Rim Nassar, Barbara Vernus, Gilles Fouret, Benedicte Goustard, François Casas, et al.. Evidence for autophagy attenuation during post-mortem maturation of hypertrophied muscle in myostatin deficient mice. 7ème congrès du club français Autophagie CFATG, Nov 2017, Paris, France. , 2017. ⟨hal-02940597⟩
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