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.

Proteomic changes in skeletal muscle of aged rats in response to resistance training

“…PARK7 expression influences myotube size and myosin expression in skeletal muscle. Moreover, their expression is critical for Akt and mTOR activities . Upregulation of two different isoforms of myosin in the YT group may have contributed to the increase in PARK7, which was not observed in the OT group.…”

Mitochondria Initiate and Regulate Sarcopenia

“…PARK7 is an antioxidant protein that limits mitochondrial damage in response to oxidative stress (12) and it regulates skeletal muscle contractile protein synthesis and hypertrophy (149). Overexpression of PARK7 reduces mitochondrial dysfunction under oxidative stress (142) which shows a direct link between autophagy and mitochondrial function.…”

Identification of genes directly responding to DLK1 signaling in Callipyge sheep

“…Park7 has been associated with diverse biological processes including oxidative stress response, transcriptional regulation and cell survival [ 86 – 88 ]. Earlier in vitro study showed the significantly larger diameters and more total sarcomeric myosin expression in the Park7 (+/+) myotubes than in the Park7 (−/−) myotubes partially due to the altered activity of the PI3K/AKT pathway [ 27 ]. The up-regulation of PARK7 in callipyge lambs may lead to the enhanced activity and/or prolonged sustained activity of the PI3K/AKT pathway and in turn to increase the response of the downstream elements in the PI3K/AKT pathway to increase protein synthesis and muscle mass.…”

“…DLK1 mRNA was up-regulated in longissimus dorsi, gluteus medius and semimembranosus , the hypertrophied muscles in callipyge lambs but not up-regulated in supraspinatus , the non-hypertrophied muscle [ 13 , 15 , 24 , 25 ]. The DLK1 protein was expressed at high levels in the myofibers of callipyge longissimus dorsi and semimembranosus but was not detected in normal muscles [ 26 , 27 ] .…”