title: Park7 expression influences myotube size and myosin expression in muscle.
abstract: Callipyge sheep exhibit postnatal muscle hypertrophy due to the up-regulation of DLK1 and/or RTL1. The up-regulation of PARK7 was identified in hypertrophied muscles by microarray analysis and further validated by quantitative PCR. The expression of PARK7 in hypertrophied muscle of callipyge lambs was confirmed to be up-regulated at the protein level. PARK7 was previously identified to positively regulate PI3K/AKT pathway by suppressing the phosphatase activity of PTEN in mouse fibroblasts. The purpose of this study was to investigate the effects of PARK7 in muscle growth and protein accretion in response to IGF1. Primary myoblasts isolated from Park7 (+/+) and Park7 (-/-) mice were used to examine the effect of differential expression of Park7. The Park7 (+/+) myotubes had significantly larger diameters and more total sarcomeric myosin expression than Park7 (-/-) myotubes. IGF1 treatment increased the mRNA abundance of Myh4, Myh7 and Myh8 between 20-40% in Park7 (+/+) myotubes relative to Park7 (-/-). The level of AKT phosphorylation was increased in Park7 (+/+) myotubes at all levels of IGF1 supplementation. After removal of IGF1, the Park7 (+/+) myotubes maintained higher AKT phosphorylation through 3 hours. PARK7 positively regulates the PI3K/AKT pathway by inhibition of PTEN phosphatase activity in skeletal muscle. The increased PARK7 expression can increase protein synthesis and result in myotube hypertrophy. These results support the hypothesis that elevated expression of PARK7 in callipyge muscle would increase levels of AKT activity to cause hypertrophy in response to the normal IGF1 signaling in rapidly growing lambs. Increasing expression of PARK7 could be a novel mechanism to increase protein accretion and muscle growth in livestock or help improve muscle mass with disease or aging.
authors.affiliation: Department of Animal Sciences, Purdue University, West Lafayette, Indiana, United States of America.
authors.forename: Hui
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Animal Sciences, Purdue University, West Lafayette, Indiana, United States of America.
authors.forename: Jolena N
authors.initials: JN
authors.lastname: Waddell
authors.affiliation: Department of Animal Sciences, Purdue University, West Lafayette, Indiana, United States of America; Center for Cancer Research, Purdue University, West Lafayette, Indiana, United States of America.
authors.forename: Shihuan
authors.initials: S
authors.lastname: Kuang
authors.affiliation: Department of Animal Sciences, Purdue University, West Lafayette, Indiana, United States of America.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Bidwell
mesh_terms: D000818:Animals; D048429:Cell Size / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005838:Genotype; D006984:Hypertrophy; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009218:Myosins / Q000235:genetics / Q000378:metabolism*; D015513:Oncogene Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D054464:Peroxiredoxins; D010766:Phosphorylation / Q000187:drug effects; D000071617:Protein Deglycase DJ-1; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012518:Sarcomeres / Q000378:metabolism; D012756:Sheep; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D015513:Oncogene Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D054464:Peroxiredoxins; D051057:Proto-Oncogene Proteins c-akt; C503466:PARK7 protein, mouse; D000071617:Protein Deglycase DJ-1; D051059:PTEN Phosphohydrolase; D009218:Myosins