MECHANISMS OF MUSCLE FUNCTION: FATIGUE AND OXIDATIVE STRESS

Abstract: 

Background: In the EU chronic kidney diseases (CKD) affect 40m people of which thousands per year progress into renal failure requiring haemodialysis or a kidney transplant to survive. Patients present with mixture of functional and structural muscle abnormalities, described as uraemic myopathy. While inflammation and oxidative stress are implicated, the available human studies do not agree on specific uraemia-induced effects on skeletal muscle molecular, metabolic and functional aspects. It is vital to systematically explore the basis for the development of muscular functional deficits and the ensuing metabolic comorbidity experienced by CKD patients.

Aim: By adopting a systems approach, we will thoroughly study uraemic muscle with the aim to reveal the mechanisms, critical factors and their interdependence behind the effects of uraemia on skeletal muscle. Emphasis will be given on understanding the emergent behaviour in fatigue and/or oxidative stress. Results will guide future "˜structure/function-informed" treatments to improve muscle function.

Work-packages: using an animal model of uraemia (WP2) we will biochemically & metabolically characterise uraemic muscle (WP3), assess morphology, motor proteins expression & post-translational modifications (WP4), and measure functional characteristics of single ureamic muscle fibres in response to fatigue (WP5) and oxidative stress (WP6). We will also test the efficacy of selected small molecules as "˜muscle tonics" (WP6). High standards in Administration (WP1) & Dissemination (WP7) will be maintained.

Expected results: Our research will constitute a tremendous progress in the understanding of the biochemical/metabolic/functional effects of renal disease. Unravelling the factors that modify the interaction and concerted action of muscle proteins in uraemia is a necessary prerequisite, if we aspire to design effective pharmaceutical or other interventions for treating muscle weakness and fatigue in CKD and other diseases.

 

Mis: 377260

Project info

Acronym:
MUSCLE-FUN
Coordinating Institution:
University of Thessaly
Scientific Coordinator:
Koutedakis Yiannis
Research Team 1 Leader:
Karatzaferi Christina
Research Team 2 Leader:
Stefanidis Ioannis
Research Team 3 Leader:
Jamurtas Athanasios
Research Team 4 Leader:
Sakkas Giorgos

Stats

I.D.:
712
Mis:
377260
Duration (months):
47
Budget:
560 987.00
Diavgeia:
ΑΔΑ: Β4ΛΔ9-8ΘΕ

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