Myofibrillar protein synthesis in myostatin-deficient mice.
Either increased protein synthesis or prolonged protein half-life is necessary to support the excessive muscle growth and maintenance of enlarged muscles in myostatin-deficient mice. This issue was addressed by determining in vivo rates of myofibrillar protein synthesis in mice with constitutive myostatin deficiency (Mstn(DeltaE3/DeltaE3)) or normal myostatin expression (Mstn(+/+)) by measuring tracer incorporation after a systemic flooding dose of l-[ring-(2)H(5)]phenylalanine. At 5-6 wk of age, Mstn(DeltaE3/DeltaE3) mice had increased muscle mass (40%), fractional rates of myofibrillar synthesis (14%), and protein synthesis per whole muscle (60%) relative to Mstn(+/+) mice. With maturation, fractional rates of synthesis declined >50% in parallel with decreased DNA and RNA [total, 28S rRNA, and poly(A) RNA] concentrations in muscle. At 6 mo of age, Mstn(DeltaE3/DeltaE3) mice had even greater increases in muscle mass (90%) and myofibrillar synthesis per muscle (85%) relative to Mstn(+/+) mice, but the fractional rate of synthesis was normal. Estimated myofibrillar protein half-life was not affected by myostatin deficiency. Muscle DNA concentrations were reduced in both young and mature Mstn(DeltaE3/DeltaE3) mice, whereas RNA concentrations were normal, so the ratio of RNA to DNA was approximately 30% greater than normal in Mstn(DeltaE3/DeltaE3) mice. Thus the increased protein synthesis and RNA content per muscle in myostatin-deficient mice cannot be explained entirely by an increased number of myonuclei.
Welle
Stephen
S
Department of Medicine in the Center for Aging and developmental Biology, University of Rochester, Rochester, NY 14642, USA. stephen_welle@urmc.rochester.edu
Bhatt
Kirti
K
Pinkert
Carl A
CA
D000818:Animals; D002401:Cathepsin B / Q000096:biosynthesis / Q000235:genetics; D004247:DNA / Q000235:genetics / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024510:Muscle Development / Q000502:physiology*; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics; D055435:Myostatin; D010649:Phenylalanine / Q000378:metabolism; D052097:Quadriceps Muscle / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D012339:RNA, Ribosomal, 28S / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms; D016212:Transforming Growth Factor beta / Q000172:deficiency* / Q000378:metabolism; D025822:Ubiquitin C / Q000096:biosynthesis / Q000235:genetics
C525912:Mstn protein, mouse; D009124:Muscle Proteins; D055435:Myostatin; D012333:RNA, Messenger; D012339:RNA, Ribosomal, 28S; D016212:Transforming Growth Factor beta; D025822:Ubiquitin C; D010649:Phenylalanine; D004247:DNA; D002401:Cathepsin B