Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
Biochem Biophys Res Commun. 2012 Jul 13;423(4):739-43. doi: 10.1016/j.bbrc.2012.06.029. Epub 2012 Jun 13.
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.
高水平的糖皮质激素会导致肌肉减少和无力。β-羟基-β-甲基丁酸（HMB）可减轻各种分解代谢状态下的肌肉质量损失，但 HMB 对糖皮质激素诱导的肌肉萎缩的影响尚不清楚。我们检验了这样一个假设，即 HMB 可防止皮质酮诱导的培养肌管萎缩。用皮质酮处理培养的 L6 肌管会导致蛋白降解增加，以及 atrogin-1 和 MuRF1 的表达增加，蛋白合成减少，肌管缩小。皮质酮的所有这些作用都被 HMB 减弱了。进一步的实验提供了证据，表明 HMB 对皮质酮诱导的蛋白降解增加和蛋白合成减少的抑制作用分别受到 p38/MAPK 和 PI3K/Akt 依赖性细胞信号的调节。这些结果表明，HMB 可以预防糖皮质激素诱导的肌肉减少。
