Branched-chain amino acids and arginine suppress MaFbx/atrogin-1 mRNA expression via mTOR pathway in C2C12 cell line.
The effect of amino acid on muscle protein degradation remains unclear. Recent studies have elucidated that proteolysis in catabolic conditions occurs through ubiquitin-proteasome proteolysis pathway and that muscle-specific ubiquitin ligases (atrogin-1 and MuRF1) play an important role in protein degradation. In the present study, we examined the direct effect of 5 mM amino acids (leucine, isoleucine, valine, glutamine and arginine) on atrogin-1 and MuRF1 levels in C2C12 muscle cells and the involved intracellular signal transduction pathway. Leucine, isoleucine and valine suppressed atrogin-1 and MuRF1 mRNA levels (approximately equal to 50%) at 6 and 24 h stimulations. Arginine showed a similar effect except at 24 h-treatment for atrogin-1 mRNA. However, glutamine failed to reduce atrogin-1 and MuRF1 mRNA levels. The inhibitory effect of leucine, isoleucine or arginine on atrogin-1 mRNA level was reversed by rapamycin, although wortmannin did not reverse the effect. PD98059 and HA89 reduced basal atrogin-1 level without influencing the inhibitory effects of those amino acids. The inhibitory effect of leucine, isoleucine or arginine on MuRF1 mRNA levels was not reversed by rapamycin. Taken together, these findings indicated that leucine, isoleucine and arginine decreased atrogin-1 mRNA levels via mTOR and that different pathways were involved in the effect of those amino acids on MuRF1 mRNA levels.
Herningtyas
Elizabeth Henny
EH
Division of Diabetes, Endocrinology, Metabolism, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Okimura
Yasuhiko
Y
Handayaningsih
Anastasia Evi
AE
Yamamoto
Daisuke
D
Maki
Taiki
T
Iida
Keiji
K
Takahashi
Yutaka
Y
Kaji
Hidesuke
H
Chihara
Kazuo
K
D000597:Amino Acids, Branched-Chain / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D002460:Cell Line; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D007546:Isoquinolines / Q000494:pharmacology; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics* / Q000378:metabolism; D013217:Starvation; D013449:Sulfonamides / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases; D013997:Time Factors; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
D000597:Amino Acids, Branched-Chain; D005419:Flavonoids; D007546:Isoquinolines; D009124:Muscle Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D013449:Sulfonamides; D000070584:Tripartite Motif Proteins; D001120:Arginine; C486691:Fbxo32 protein, mouse; D044843:SKP Cullin F-Box Protein Ligases; C499084:Trim63 protein, mouse; D044767:Ubiquitin-Protein Ligases; D011494:Protein Kinases; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one