Administration of a mutated myostatin propeptide to neonatal mice significantly enhances skeletal muscle growth.
Myostatin is a dominant inhibitor of skeletal muscle development and growth. As transgenic over-expression of myostatin propeptide dramatically enhanced muscle mass, we hypothesized that administration of myostatin propeptide will increase muscle growth. In this study, the wild-type form of porcine myostatin propeptide and its mutated form at the cleavage site of metalloproteinases of BMP-1/TLD family were produced from insect cells. In vitro A204 cells reporter assays showed that both wild-type and the mutated propeptides depressed myostatin activity. The recombinant propeptides at four-fold myostatin concentration can effectively block myostatin function during co-incubation with A204 cells. In particular, the mutated propeptide appeared much more effective than wild-type propeptide over a long period during the in vitro co-incubation. Administration of the mutated propeptide to neonatal mice at the age of 11 and 18 days was tested and showed significant increase in growth performance by 11-15% from the age of 25 to 57 days (P < 0.05). The major skeletal muscles of mice that were injected with mutated propeptide were 13.5-24.8% heavier than the control group (P < 0.05) as a result of muscle fiber hypertrophy. In conclusion, administration of the mutated myostatin propeptide during the neonatal period is an effective way for promoting muscle growth.
Li
Zicong
Z
Department of Human Nutrition, Food and Animal Sciences, University of Hawaii, Honolulu, Hawaii.
Zhao
Baoping
B
Kim
Yong Soo
YS
Hu
Ching Yuan
CY
Yang
Jinzeng
J
D000818:Animals; D000831:Animals, Newborn; D002460:Cell Line; D005260:Female; D006801:Humans; D007313:Insecta; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000187:drug effects / Q000254:growth & development; D009154:Mutation; D055435:Myostatin / Q000235:genetics / Q000494:pharmacology; D011498:Protein Precursors / Q000235:genetics / Q000494:pharmacology; D013552:Swine
D055435:Myostatin; D011498:Protein Precursors