Carnosine synthase deficiency in mice affects protein metabolism in skeletal muscle
Carnosine synthase deficiency in mice affects protein metabolism in skeletal muscle
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DOI：
10.1016/j.bbrc.2022.04.075
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发表时间：
2022-04-29
影响因子：
3.1
通讯作者：
Nishimura, Toshihide
中科院分区：
文献类型：
--
作者：
Wu, Jiawei;Egusa, Ai;Nishimura, Toshihide
肌肽和鹅氨酸是在许多脊椎动物的骨骼肌和神经系统中发现的丰富的肽。多项体外和体内研究表明，外源性肌肽可改善运动表现。此外，肌肽是一种抗氧化剂和抗疲劳补充剂。然而，内源性肌肽及其相关的含组氨酸二肽在生物体内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。我们发现肌肽合酶敲除小鼠的骨骼肌中检测不到肌肽和鹅肽。我们还量化了肌肉蛋白质代谢中的蛋白质基因表达和酶水平。肌肽合成酶基因缺陷小鼠的肌肉蛋白合成胰岛素样生长因子-1 (IGF-1) 和降解酶组织蛋白酶 B 的基因和蛋白质水平显着低于野生型小鼠。与野生型小鼠相比，肌肽合酶基因缺陷小鼠在强迫运动中的 3-甲基组氨酸（肌肉蛋白水解标志物）含量和腓肠肌重量显着降低。因此，我们发现肌肽缺乏会影响骨骼肌的体重维持和蛋白质代谢，表明肌肽调节骨骼肌蛋白质代谢。 (c) 2022 作者。由爱思唯尔公司出版
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 car-nosine improves exercise performance. Furthermore, carnosine is an antioxidant and antifatigue sup-plement. 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. (c) 2022 The Authors. Published by Elsevier Inc.