Department of Surgery, University of Cincinnati College of Medicine, and Shriners Hospital for Children, 231 Albert Sabin Way, Cincinnati, OH 45267-0558, USA.
Peptides. 2009 Oct;30(10):1909-13. doi: 10.1016/j.peptides.2009.06.029. Epub 2009 Jul 3.
Thermal injury results in hypermetabolism, loss of body weight, and skeletal muscle wasting in mice and rats. Our earlier studies have demonstrated that ghrelin injection stimulates food intake and growth hormone release and inhibits skeletal muscle proteolysis in rats with thermal injury. We sought to develop a lower molecular weight, stable and longer acting peptide to combat the catabolic responses caused by thermal injury. Towards this goal, we examined the role of the hexapeptide mimetic of ghrelin, growth hormone-releasing peptide-2 (GHRP-2), on expression of E3 ubiquitin ligases and breakdown of muscle protein in rats with thermal injury. Slow in vivo release of GHRP-2 through minipump for 24h attenuated the thermal injury-induced increase in mRNA expression of IL-6 and of the E3 ubiquitin ligases, MuRF-1 and MAFbx, in rat skeletal muscle. Furthermore, burn-induced increases in total and myofibrillar protein breakdown from rat EDL muscle were attenuated by GHRP-2. These findings suggest that catabolic responses resulting from thermal injury can be attenuated by GHRP-2.
热损伤可导致小鼠和大鼠代谢亢进、体重减轻和骨骼肌耗损。我们之前的研究表明，ghrelin 注射可刺激食物摄入和生长激素释放，并抑制热损伤大鼠的骨骼肌蛋白水解。我们试图开发一种低分子量、稳定且长效的肽来对抗热损伤引起的分解代谢反应。为此，我们研究了 ghrelin 的六肽模拟物、生长激素释放肽-2（GHRP-2）在热损伤大鼠中对 E3 泛素连接酶表达和肌肉蛋白分解的作用。通过迷你泵在体内缓慢释放 GHRP-2 24 小时可减轻热损伤引起的大鼠骨骼肌中 IL-6 和 E3 泛素连接酶 MuRF-1 和 MAFbx 的 mRNA 表达增加。此外，GHRP-2 可减轻烧伤引起的大鼠 EDL 肌肉总蛋白和肌原纤维蛋白分解增加。这些发现表明，GHRP-2 可减轻热损伤引起的分解代谢反应。
