Personal Webpage Anthony MJ Sanchez

Abbreviations:

AICAR, 5-aminoimidazole-4-carboxamide-1-ß-4-ribofuranoside; AMPK, adenosine monophosphate-activated protein kinase; eIF3f, eukaryotic initiation factor 3 subunit f; FoxO, Forkhead box other class; MAFbx/atrogin1, muscle atrophy F-box; mTORC1, mammalian target of rapamycin complex 1; S6K1, ribosomal protein S6 kinase 1; Ulk1, unc-51-like kinase 1

4/ Ergogenic effects of β2 agonists

The last line of research is devoted to human physiology. We studied the effects of β2 agonists that have an action on the signaling pathways presented. Specifically we sought to characterize the ergogenic effects of two β2 agonists, salbutamol and terbutaline in non-asthmatic athletes. This work is of interest in anti-doping in the extent β2 agonists remain a research priority for WADA. In a first study, we demonstrated that salbutamol can improve sprint performance after two treatments, taken immediately before exercise, and long-term treatment (3 weeks) to doses equivalent to what can be given up in a therapeutic setting. We reported that the acute intake allowed a greater improvement in performance than the long-term treatment which is associated with reduced sensitivity to β2 agonists. In a second study, we showed that oral administration of terbutaline (supratherapeutic dose, 8 mg) did not have any ergogenic effect. Indeed no improvement in anaerobic and aerobic performance were found following treatment, but we observed side effects that may explain the lack of ergogenic effect. These work have resulted in two publications in the

European Journal of Applied Physiology

and one paper in

Movement & Sport Sciences - Science & Motricité

.

3/ Optimization of athlete performance and Modeling of training responses

A third line of research focuses on modeling the effects of sports training. An article in which we modeled the responses to the training of elite gymnasts, and in which we performed simulations of taper strategies has been published in the

Journal of Sports Sciences

. Another study aimed to model the responses to resistance training in rat and has been published in

BioMed Research International

.

Actual projects aim to investigate modeling in mountain sports.

2/ Regulation of skeletal muscle mass by the translation initiation factor eIF3f

In a complementary project, we are interested in the molecular mechanisms involved in hypertrophy induced by mTORC1 complex and its partners. We have shown that (i) the presence of a TOS motif located on the C-terminal part of the initiation factor of translation eIF3f is essential to connect mTORC1 to its target S6K1 and 4E-BP1, (ii) the degradation of eIF3f by MAFbx inhibits activation of mTOR by S6K1 and (iii) over-expression of a mutant of eIF3f insensitive to MAFbx degradation leads to an increase in the assembly of the pre-initiation complex and the CAP-dependent translation during atrophy. This work has been published in the journals

Plos One

and

The International Journal of Biochemistry & Cell Biology

.

I drive two types of work. The first attempts to characterize the cellular mechanisms regulating skeletal muscle mass and the second is devoted to human physiology in a context of physical exercise and sport performance.

Research themes:

Research activity

1/ Autophagy pathway, exercice and nutrition

A first axis aims to better understand the role played by the metabolic sensor system represented by AMPK on the regulation of processes regulating skeletal muscle protein synthesis and protein degradation, especially the FoxO-related pathway and the autophagy-lysosomal system. A part of this work, published in the

Journal of Cellular Biochemistry,

in the

American Journal of Physiology - Cell Physiology

and

Cellular and Molecular Life Sciences

, shows that AMPK has a dual action on the processes regulating muscle mass. AMPK inhibits protein translation through repression of mTOR activity and its targets S6K1 and 4E-BP1, and increased protein degradation through increased autophagic flux and the activity of the ubiquitin-proteasome system. We identified the protein Ulk1 as a new target of AMPK. Furthermore, we also demonstrated that AMPK regulates the activity of systems degradation by modulating the activity of the transcription factor FOXO3a.

A study recently published in

Medicine & Science in Sports & Exercise

, aimed to characterize the modulation of protein turnover, autophagy and mitochondrial dynamics during conventional exercises. We showed that exercise quickly initiates autophagy (

i.e.

UlK1 axis), with an increase of autophagic flux near to exhaustion. A rise in the phosphorylation of DRP1, a GTPase essential for mitochondrial fission, was quickly found during exercise without any change in the expression of the fusion markers OPA1 and Mitofusin-2. Also, we found that exercise decreases the activity of the Akt/MTOR/4E-BP1 pathway from 90 min of exercise corresponding to approximatively 40-50% of VO2max. It is conceivable that the involvement of the autophagic system, including mitophagy (

i.e.

mitochondrial autophagy), in response to exercise must be considered not only in muscle homeostasis during exercise but also in disease, including metabolic and muscle disorders.