Impact of short- and long-term electrically induced muscle exercise on gene signaling pathways, gene expression, and PGC1a methylation in men with spinal cord injury

Abstract

Exercise attenuates the development of chronic noncommunicable diseases (NCDs). Gene signaling pathway analysis offers an opportunity to discover if electrically induced muscle exercise regulates key pathways among people living with spinal cord injury (SCI). We examined short-term and long-term durations of electrically induced skeletal muscle exercise on complex gene signaling pathways, specific gene regulation, and epigenetic tagging of PGC1a, a major transcription factor in skeletal muscle of men with SCI. After short- or long-term electrically induced exercise training, participants underwent biopsies of the trained and untrained muscles. RNA was hybridized to an exon microarray and analyzed by a gene set enrichment analysis. We discovered that long-term exercise training regulated the Reactome gene sets for metabolism (38 gene sets), cell cycle (36 gene sets), disease (27 gene sets), gene expression and transcription (22 gene sets), organelle biogenesis (4 gene sets), cellular response to stimuli (8 gene sets), immune system (8 gene sets), vesicle-mediated transport (4 gene sets), and transport of small molecules (3 gene sets). Specific gene expression included: oxidative catabolism of glucose including PDHB ( P < 0.001), PDHX ( P < 0.001), MPC1 ( P < 0.009), and MPC2 ( P < 0.007); Oxidative phosphorylation genes including SDHA ( P < 0.006), SDHB ( P < 0.001), NDUFB1 ( P < 0.002), NDUFA2 ( P < 0.001); transcription genes including PGC1α ( P < 0.030) and PRKAB2 ( P < 0.011); hypertrophy gene MSTN ( P < 0.001); and the myokine generating FNDC5 gene ( P < 0.008). Long-term electrically induced exercise demethylated the major transcription factor PGC1a. Taken together, these findings support that long-term electrically induced muscle activity regulates key pathways associated with muscle health and systemic metabolism.