Kynurenine aminotransferase isoforms display fiber-type specific expression in young and old human skeletal muscle

V L Wyckelsma; W Lindkvist; T Venckunas; M Brazaitis; S Kamandulis; M Pääsuke; J Ereline; H Westerblad; D C Andersson

doi:10.1016/j.exger.2020.110880

Kynurenine aminotransferase isoforms display fiber-type specific expression in young and old human skeletal muscle

Exp Gerontol. 2020 Feb 15:134:110880. doi: 10.1016/j.exger.2020.110880. Online ahead of print.

Authors

V L Wyckelsma¹, W Lindkvist¹, T Venckunas², M Brazaitis², S Kamandulis², M Pääsuke³, J Ereline³, H Westerblad⁴, D C Andersson⁵

Affiliations

¹ Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
² Institute of Sport Science and Innovations, Lithuanian Sports University, Kaunas, Lithuania.
³ Institute of Sport Sciences and Physiotherapy, Faculty of Medicine, University of Tartu, Estonia.
⁴ Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Institute of Sport Science and Innovations, Lithuanian Sports University, Kaunas, Lithuania.
⁵ Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Heart, Vascular and Neurology Theme, Section for Cardiology, Karolinska University Hospital, Stockholm, Sweden. Electronic address: daniel.c.andersson@ki.se.

PMID: 32068089
DOI: 10.1016/j.exger.2020.110880

Abstract

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.

Keywords: Aging; Kynurenine aminotransferases; Mitochondria; Muscle fiber-type; Skeletal muscle.