Wyckelsma V L, Lindkvist W, Venckunas T, Brazaitis M, Kamandulis S, Pääsuke M, Ereline J, Westerblad H, Andersson D C
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Institute of Sport Science and Innovations, Lithuanian Sports University, Kaunas, Lithuania.
Exp Gerontol. 2020 Feb 15;134:110880. doi: 10.1016/j.exger.2020.110880.
Conversion of kynurenine (KYN) to kynurenic acid (KYNA) is the main pathway for free tryptophan degradation in skeletal muscle and has emerged as an important mechanism of how exercise is linked to promotion of mental health. Metabolism of KYN to KYNA mainly depends on the expression of kynurenine aminotransferases (KATs) that is under control of the mitochondria biogenesis regulator PGC-1α. We therefore hypothesized that expression of KATs would vary between muscle fibers that differ in mitochondrial content, i.e. oxidative type I vs more glycolytic type II muscle fibers. Moreover, we tested the hypothesis that KAT expression differs with age. Single muscle fibers were isolated from biopsies taken from the vastus lateralis muscle in young and old healthy subjects. In young and old subjects the abundance of KAT I, KAT III and KAT IV was greater in Type I than Type II fibers without age-dependent difference in the KAT isoform expressions. The link to mitochondrial content was further seen as the expression of KAT IV correlated to mitochondrial cytochrome c oxidase IV (COX IV) abundance in both fiber types. In conclusion, we describe for the first time the expression pattern of KAT isoforms with respect to specific fiber types and age in human skeletal muscle.
犬尿氨酸（KYN）向犬尿酸（KYNA）的转化是骨骼肌中游离色氨酸降解的主要途径，并且已成为运动与促进心理健康之间联系的重要机制。KYN向KYNA的代谢主要取决于犬尿氨酸转氨酶（KATs）的表达，而KATs的表达受线粒体生物发生调节因子PGC-1α的控制。因此，我们推测KATs的表达在具有不同线粒体含量的肌纤维之间会有所不同，即氧化型I型肌纤维与更多糖酵解型II型肌纤维。此外，我们检验了KAT表达随年龄变化的假设。从年轻和老年健康受试者的股外侧肌活检组织中分离出单根肌纤维。在年轻和老年受试者中，I型纤维中KAT I、KAT III和KAT IV的丰度高于II型纤维，KAT同工型表达不存在年龄依赖性差异。KAT IV的表达与两种纤维类型中的线粒体细胞色素c氧化酶IV（COX IV）丰度相关，这进一步表明了与线粒体含量的联系。总之，我们首次描述了人骨骼肌中KAT同工型相对于特定纤维类型和年龄的表达模式。
