Branched-chain amino acids inhibit proteolysis in rat skeletal muscle: mechanisms involved.
Incubation of isolated rat soleus and EDL muscles in the presence of 10 mM leucine resulted in a decreased proteolytic rate as measured by the release of tyrosine into the incubation medium. The effect of this branched-chain amino acid (BCAA) is associated with a decreased activity of the lysosomal proteases and a decreased expression of the genes of the ATP-ubiquitin-dependent proteolysis (ubiquitin and C8). Incubation of muscles in the presence of actinomycin D revealed that the effects of the amino acid can be accounted for by an inhibition of the transcription rate. The presence of leucine did not influence the gene expression of other nonlysosomal (m-calpain) and lysosomal (cathepsin B) proteolytic systems. It is concluded that the well-known effect of BCAA on muscle proteolysis is mediated, in the short term, by the inhibition of lysosomal proteolysis. In a longer period, based on the inhibition of gene transcription observed, an involvement of the ATP-dependent proteolytic system is also likely to occur.
Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain.
S
S
Busquets
B
B
Alvarez
M
M
Llovera
N
N
Agell
F J
FJ
López-Soriano
J M
JM
Argilés
D000255:Adenosine Triphosphate / Q000378:metabolism; D000597:Amino Acids, Branched-Chain / Q000494:pharmacology*; D000818:Animals; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism
D000597:Amino Acids, Branched-Chain; D011480:Protease Inhibitors; D012333:RNA, Messenger; D014452:Ubiquitins; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D010450:Endopeptidases