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Expression of microRNAs and target proteins in skeletal muscle of rats selectively bred for high and low running capacity

Pinto, SK and Lamon, S and Stephenson, EJ and Kalanon, M and Mikovic, J and Koch, LG and Britton, SL and Hawley, JA and Camera, DM (2017) Expression of microRNAs and target proteins in skeletal muscle of rats selectively bred for high and low running capacity. American Journal of Physiology-Endocrinology and Metabolism, 313 (3). ISSN 0193-1849

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Abstract

Impairments in mitochondrial function and substrate metabolism are implicated in the etiology of obesity and Type 2 diabetes. MicroRNAs (miRNAs) can degrade mRNA or repress protein translation and have been implicated in the development of such disorders. We used a contrasting rat model system of selectively bred high- (HCR) or low- (LCR) intrinsic running capacity with established differences in metabolic health to investigate the molecular mechanisms through which miRNAs regulate target proteins mediating mitochondrial function and substrate oxidation processes. Quantification of select miRNAs using the rat miFinder miRNA PCR array revealed differential expression of 15 skeletal muscles (musculus tibialis anterior) miRNAs between HCR and LCR rats (14 with higher expression in LCR; P < 0.05). Ingenuity Pathway Analysis predicted these altered miRNAs to collectively target multiple proteins implicated in mitochondrial dysfunction and energy substrate metabolism. Total protein abundance of citrate synthase (CS; miR-19 target) and voltage-dependent anion channel 1 (miR-7a target) were higher in HCR compared with LCR cohorts (~57 and ~26%, respectively; P < 0.05). A negative correlation was observed for miR-19a-3p and CS (r = 0.32, P = 0.015) protein expression. To determine whether miR-19a-3p can regulate CS in vitro, we performed luciferase reporter and transfection assays in C2C12 myotubes. MiR-19a-3p binding to the CS untranslated region did not change luciferase reporter activity; however, miR-19a-3p transfection decreased CS protein expression (∼70%; P < 0.05). The differential miRNA expression targeting proteins implicated in mitochondrial dysfunction and energy substrate metabolism may contribute to the molecular basis, mediating the divergent metabolic health profiles of LCR and HCR rats

Item Type: Article
Uncontrolled Keywords: 06 Biological Sciences, 11 Medical And Health Sciences
Subjects: R Medicine > RC Internal medicine > RC1200 Sports Medicine
Divisions: Sport & Exercise Sciences
Publisher: Amercian Physiological Society
Related URLs:
Date Deposited: 30 Oct 2017 09:49
Last Modified: 30 Oct 2017 09:49
DOI or Identification number: 10.1152/ajpendo.00043.2017
URI: http://researchonline.ljmu.ac.uk/id/eprint/7427

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