Abstract
The complement 1q binding protein C (C1QBP), also known as p32, is highly expressed in rapidly growing tissues and plays a crucial role in cell proliferation and apoptosis. However, there are no data interpreting its mechanisms in muscle development. To investigate the role of p32 in sheep muscle development, an 856 bp cDNA fragment of p32 containing an 837 bp coding sequence that encodes 278 amino acids was analyzed. We then revealed that the expression of p32 in the longissimus and quadricep muscles of fetal sheep was more significantly up-regulated than expression at other developmental stages. Furthermore, we found that the expression of p32 was increased during myoblasts differentiation in vitro. Additionally, the knockdown of p32 in sheep myoblasts effectively inhibited myoblast differentiation, proliferation, and promoted cell apoptosis in vitro. The interference of p32 also changed the energy metabolism from Oxidative Phosphorylation (OXPHOS) to glycolysis and activated AMP-activated protein kinase (AMPK) phosphorylation in sheep myoblasts in vitro. Taken together, our data suggest that p32 plays a vital role in the development of sheep muscle and provides a potential direction for future research on muscle development and some muscle diseases.
Highlights
Skeletal muscle accounts for about 40% of the body’s weight, and has many functions, such as maintaining energy requirements, maintaining posture, and protecting soft tissues
The RNA-seq data showed that the expression of p32 in the longissimus muscle of fetal sheep was significantly higher than that in postnatal sheep muscle [7], so we hypothesized that p32 may play a crucial role during the skeletal muscle development of sheep
The knocking down of p32 in myoblasts decreased the cellular ATP level. These results indicated that a lack of p32 in myoblasts could change the cellular metabolism from Oxidative Phosphorylation (OXPHOS) to glycolysis and reduce ATP production significantly
Summary
Skeletal muscle accounts for about 40% of the body’s weight, and has many functions, such as maintaining energy requirements, maintaining posture, and protecting soft tissues. The RNA-seq data showed that the expression of p32 in the longissimus muscle of fetal sheep was significantly higher than that in postnatal sheep muscle [7], so we hypothesized that p32 may play a crucial role during the skeletal muscle development of sheep. Infants with biallelic C1QBP mutations presented with cardiomyopathy accompanied by multisystemic involvement (liver, kidney, and brain), and children and adults presented with myopathy They all present with multiple OXPHOS deficiencies [20]. AMPK is a highly conserved sensor of cellular energy status that could be activated under low intracellular ATP conditions [22] and is involved in cell growth, proliferation, apoptosis, autophagy, and other basic biological processes [23]. P32 is highly expressed in rapidly growing tissues, such as the skeletal muscle of fetal sheep. This study lays the foundation for exploring the role of p32 in muscle development and its potential mechanisms
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