Skeletal muscle Heat shock protein 60 increases after endurance training and induces peroxisome proliferator-activated receptor gamma coactivator 1 α1 expression.

Rosario Barone,Dario Coletti,Claudia Campanella,Felicia Farina,Filippo Macaluso,Everly Conway De Macario,Alberto Jl Macario,Giovanni Zummo,Claudia Sangiorgi,Antonella Marino Gammazza,Viviana Moresi,Sergio Adamo,Valentina Di Felice,Francesco Cappello

doi:10.1038/srep19781

Abstract

Heat shock protein 60 (Hsp60) is a chaperone localizing in skeletal muscle mitochondria, whose role is poorly understood. In the present study, the levels of Hsp60 in fibres of the entire posterior group of hindlimb muscles (gastrocnemius, soleus, and plantaris) were evaluated in mice after completing a 6-week endurance training program. The correlation between Hsp60 levels and the expression of four isoforms of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α) were investigated only in soleus. Short-term overexpression of hsp60, achieved by in vitro plasmid transfection, was then performed to determine whether this chaperone could have a role in the activation of the expression levels of PGC1α isoforms. The levels of Hsp60 protein were fibre-type specific in the posterior muscles and endurance training increased its content in type I muscle fibers. Concomitantly with the increased levels of Hsp60 released in the blood stream of trained mice, mitochondrial copy number and the expression of three isoforms of PGC1α increased. Overexpressing hsp60 in cultured myoblasts induced only the expression of PGC1 1α, suggesting a correlation between Hsp60 overexpression and PGC1 1 α activation.

Highlights

The chaperoning system participates in many cellular functions from assisting protein folding and assembling of multimolecular complexes to maintaining the correct shape of enzymes[1,2,3,4,5,6,7]
Trained groups for 30 and 45 days (TR30 and TR45, respectively) and sedentary groups for 30 and 45 days (SED30 and SED45, respectively) showed a significant increase in the body weight compared to trained groups for 15 days (TR15) and sedentary groups for 15 days (SED15), respectively (P < 0.001); while the body weight of TR45 and SED45 mice increased significantly compared to TR30 and SED30 mice, respectively (P < 0.001)
The data reported here show a differential quantitative distribution of heat shock protein (Hsp)[60] within a single muscle group and changes in this pattern in response to exercise, including its increase in circulation. These data, along with what is known on the diversity of functions of Hsp[60] inside and outside cells, provide the tenets for future investigation on the role of the chaperone in muscle physiology and pathology beyond its canonical tasks inside mitochondria

Summary

Introduction

The chaperoning system participates in many cellular functions from assisting protein folding and assembling of multimolecular complexes to maintaining the correct shape of enzymes[1,2,3,4,5,6,7]. Extracellular chaperones contribute to the intercommunication between different cells, tissues, and organs[8,9,10] It follows that exercise, which requires the participation of various intercommunicating muscle-cell types and intracellular components is most likely dependent on the chaperoning system, or at least some of its components. To deal with the second question we investigated the peroxisome proliferation-activated receptor-γ (PPAR-γ ) coactivator-1α (PGC1α ) We focused on this molecule because it is a dominant regulator of oxidative metabolism, acting as a transcriptional co-activator of nuclear receptors and other transcription factors regulating mitochondrial biogenesis[13]. If that were to be the case, it would be possible to plan experiments to dissect the molecular interactions involving Hsp[60] in muscle and, by extension, to think of ways to manipulate this chaperone for improving muscle function in ageing people, and patients with cachexia and skeletal muscle disorders

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Results

Conclusion