Time‐dependent reduction in oxidative capacity among cultured myotubes from spinal cord injured individuals

Author:

Stevanovic Stanislava1ORCID,Dalmao‐Fernandez Andrea1,Mohamed Derya1,Nyman Tuula A.2,Kostovski Emil34,Iversen Per Ole56,Savikj Mladen7,Nikolic Natasa1,Rustan Arild C.1,Thoresen G. Hege18,Kase Eili T.1

Affiliation:

1. Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy University of Oslo Oslo Norway

2. Department of Immunology, Institute of Clinical Medicine University of Oslo and Oslo University Hospital Oslo Norway

3. Vestre Viken Hospital Trust Drammen Norway

4. Manifestsenteret Røyken Norway

5. Department of Nutrition, IMB University of Oslo Oslo Norway

6. Department of Hematology Oslo University Hospital Oslo Norway

7. Department of Molecular Medicine and Surgery Karolinska Institute Stockholm Sweden

8. Department of Pharmacology, Institute of Clinical Medicine University of Oslo Oslo Norway

Abstract

AbstractBackgroundSkeletal muscle adapts in reaction to contractile activity to efficiently utilize energy substrates, primarily glucose and free fatty acids (FA). Inactivity leads to atrophy and a change in energy utilization in individuals with spinal cord injury (SCI). The present study aimed to characterize possible inactivity‐related differences in the energy metabolism between skeletal muscle cells cultured from satellite cells isolated 1‐ and 12‐months post‐SCI.MethodsTo characterize inactivity‐related disturbances in spinal cord injury, we studied skeletal muscle cells isolated from SCI subjects. Cell cultures were established from biopsy samples from musculus vastus lateralis from subjects with SCI 1 and 12 months after the injury. The myoblasts were proliferated and differentiated into myotubes before fatty acid and glucose metabolism were assessed and gene and protein expressions were measured.ResultsThe results showed that glucose uptake was increased, while oleic acid oxidation was reduced at 12 months compared to 1 month. mRNA expressions of PPARGC1α, the master regulator of mitochondrial biogenesis, and MYH2, a determinant of muscle fiber type, were significantly reduced at 12 months. Proteomic analysis showed reduced expression of several mitochondrial proteins.ConclusionIn conclusion, skeletal muscle cells isolated from immobilized subjects 12 months compared to 1 month after SCI showed reduced fatty acid metabolism and reduced expression of mitochondrial proteins, indicating an increased loss of oxidative capacity with time after injury.

Publisher

Wiley

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