Wu Jiawei, Egusa Ai, Nishimura Toshihide
Department of Food Nutrition, Kagawa Nutrition University, Chiyoda, Sakado, Saitama, Japan.
Department of Food Science and Technology, Nippon Veterinary and Life Science University, Kyonancho, Musashino, Tokyo, Japan.
Biochem Biophys Res Commun. 2022 Jul 5;612:22-29. doi: 10.1016/j.bbrc.2022.04.075. Epub 2022 Apr 19.
Carnosine and anserine are abundant peptides found in the skeletal muscle and nervous system in many vertebrates. Several in vitro and in vivo studies have demonstrate that exogenously administered carnosine improves exercise performance. Furthermore, carnosine is an antioxidant and antifatigue supplement. However, the physiological functions of endogenous carnosine and its related histidine-containing dipeptides in a living organism remain unclear. We aimed to clarify the physiological roles of endogenous carnosine by investigating the characteristics of carnosine synthase gene-deficient mice and the effects of carnosine on skeletal muscle protein metabolism. We discovered that carnosine and anserine were undetectable in the skeletal muscle of carnosine synthase knockout mice. We also quantified protein gene expression and enzyme levels in muscle protein metabolism. Gene and protein levels of the muscle protein synthesizer insulin-like growth factor-1 (IGF-1) and the degrading enzyme cathepsin B were markedly lower in carnosine synthase gene-deficient mice than those in wild-type mice. The amount of 3-methylhistidine (a marker for muscle proteolysis) in forced exercise and the weight of the gastrocnemius muscle were considerably lower in carnosine synthase gene-deficient mice than in wild-type mice. Consequently, we showed that carnosine deficiency affects weight maintenance and protein metabolism in skeletal muscle, suggesting that carnosine regulates skeletal muscle protein metabolism.
肌肽和鹅肌肽是在许多脊椎动物的骨骼肌和神经系统中大量存在的肽类。多项体外和体内研究表明，外源性给予肌肽可改善运动表现。此外，肌肽是一种抗氧化和抗疲劳补充剂。然而，内源性肌肽及其相关含组氨酸二肽在生物体中的生理功能仍不清楚。我们旨在通过研究肌肽合酶基因缺陷小鼠的特征以及肌肽对骨骼肌蛋白质代谢的影响，来阐明内源性肌肽的生理作用。我们发现，在肌肽合酶基因敲除小鼠的骨骼肌中检测不到肌肽和鹅肌肽。我们还对肌肉蛋白质代谢中的蛋白质基因表达和酶水平进行了定量分析。与野生型小鼠相比，肌肽合酶基因缺陷小鼠中肌肉蛋白质合成因子胰岛素样生长因子-1（IGF-1）和降解酶组织蛋白酶B的基因和蛋白质水平明显较低。在强迫运动中，肌肽合酶基因缺陷小鼠的3-甲基组氨酸（肌肉蛋白水解的标志物）含量和腓肠肌重量均明显低于野生型小鼠。因此，我们表明肌肽缺乏会影响骨骼肌的体重维持和蛋白质代谢，这表明肌肽调节骨骼肌蛋白质代谢。
