β-Hydroxy-β-methylbutyrate (HMB) prevents dexamethasone-induced myotube atrophy.
High levels of glucocorticoids result in muscle wasting and weakness. β-hydroxy-β-methylbutyrate (HMB) attenuates the loss of muscle mass in various catabolic conditions but the influence of HMB on glucocorticoid-induced muscle atrophy is not known. We tested the hypothesis that HMB prevents dexamethasone-induced atrophy in cultured myotubes. Treatment of cultured L6 myotubes with dexamethasone resulted in increased protein degradation and expression of atrogin-1 and MuRF1, decreased protein synthesis and reduced myotube size. All of these effects of dexamethasone were attenuated by HMB. Additional experiments provided evidence that the inhibitory effects of HMB on dexamethasone-induced increase in protein degradation and decrease in protein synthesis were regulated by p38/MAPK- and PI3K/Akt-dependent cell signaling, respectively. The present results suggest that glucocorticoid-induced muscle wasting can be prevented by HMB.
Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
Zaira
Z
Aversa
Nima
N
Alamdari
Estibaliz
E
Castillero
Maurizio
M
Muscaritoli
Filippo
F
Rossi Fanelli
Per-Olof
PO
Hasselgren
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects*; D002460:Cell Line; D003907:Dexamethasone / Q000009:adverse effects*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D009124:Muscle Proteins / Q000378:metabolism; D018908:Muscle Weakness / Q000139:chemically induced / Q000517:prevention & control; D009133:Muscular Atrophy / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D014176:Protein Biosynthesis / Q000187:drug effects; D059748:Proteolysis / Q000187:drug effects; D051381:Rats; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D014631:Valerates / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D009124:Muscle Proteins; D000070584:Tripartite Motif Proteins; D014631:Valerates; C004961:beta-hydroxyisovaleric acid; D003907:Dexamethasone; C486691:Fbxo32 protein, mouse; D044843:SKP Cullin F-Box Protein Ligases; C499084:Trim63 protein, mouse; D044767:Ubiquitin-Protein Ligases