Feng Fei, Cui Bingqing, Fang Li, Lan Ting, Luo Kai, Xu Xin, Lu Zhongbing
School of Exercise and Health, Shanghai University of Sport, Shanghai 200438, China.
College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, China.
Antioxidants (Basel). 2023 Sep 13;12(9):1754. doi: 10.3390/antiox12091754.
Nitric oxide (NO) is an important biological signaling molecule affecting muscle regeneration. The activity of NO synthase (NOS) is regulated by dimethylarginine dimethylaminohydrolase 1 (DDAH1) through degradation of the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA). To investigate the role of DDAH1 in muscle injury and regeneration, muscle-specific -knockout mice () and their littermates () were used to examine the progress of cardiotoxin (CTX)-induced muscle injury and subsequent muscle regeneration. After CTX injection, mice developed more severe muscle injury than mice. Muscle regeneration was also delayed in mice on Day 5 after CTX injection. These phenomena were associated with higher serum ADMA and LDH levels as well as a great induction of inflammatory response, oxidative stress and cell apoptosis in the gastrocnemius (GA) muscle of mice. In the GA muscle of CTX-treated mice, deficiency decreased the protein expression of M-cadherin, myogenin, Bcl-2, peroxiredoxin 3 (PRDX3) and PRDX5, and increased the protein expression of MyoD, TNFα, Il-6, iNOS and Bax. In summary, our data suggest that DDAH1 exerts a protective role in muscle injury and regeneration.
一氧化氮（NO）是一种影响肌肉再生的重要生物信号分子。一氧化氮合酶（NOS）的活性由二甲基精氨酸二甲胺水解酶1（DDAH1）通过降解内源性NOS抑制剂不对称二甲基精氨酸（ADMA）来调节。为了研究DDAH1在肌肉损伤和再生中的作用，利用肌肉特异性基因敲除小鼠（）及其同窝小鼠（）来检测心脏毒素（CTX）诱导的肌肉损伤进程以及随后的肌肉再生情况。注射CTX后，基因敲除小鼠比野生型小鼠出现更严重的肌肉损伤。在注射CTX后第5天，基因敲除小鼠的肌肉再生也延迟。这些现象与基因敲除小鼠血清中更高的ADMA和LDH水平以及腓肠肌（GA）中炎症反应、氧化应激和细胞凋亡的强烈诱导有关。在CTX处理小鼠的GA肌肉中，基因敲除降低了M-钙黏蛋白、肌细胞生成素、Bcl-2、过氧化物酶3（PRDX3）和PRDX5的蛋白表达，并增加了MyoD、TNFα、Il-6、诱导型一氧化氮合酶（iNOS）和Bax的蛋白表达。总之，我们的数据表明DDAH1在肌肉损伤和再生中发挥保护作用。
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