L-tyrosine supplementation does not ameliorate skeletal muscle dysfunction in zebrafish and mouse models of dominant skeletal muscle α-actin nemaline myopathy.

Autor: Messineo AM; Centre for Medical Research, The University of Western Australia, Perth, Western Australia, Australia.; Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, Western Australia, Australia., Gineste C; Aix-Marseille University, CNRS, CRMBM, Marseille, France., Sztal TE; School of Biological Sciences, Monash University, Melbourne, Australia., McNamara EL; Centre for Medical Research, The University of Western Australia, Perth, Western Australia, Australia.; Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, Western Australia, Australia., Vilmen C; Aix-Marseille University, CNRS, CRMBM, Marseille, France., Ogier AC; Aix-Marseille University, CNRS, CRMBM, Marseille, France., Hahne D; Centre for Microscopy, Characterisation and Analysis, The University of Western Australia, Perth, Western Australia, Australia., Bendahan D; Aix-Marseille University, CNRS, CRMBM, Marseille, France., Laing NG; Centre for Medical Research, The University of Western Australia, Perth, Western Australia, Australia.; Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, Western Australia, Australia., Bryson-Richardson RJ; School of Biological Sciences, Monash University, Melbourne, Australia., Gondin J; Aix-Marseille University, CNRS, CRMBM, Marseille, France.; Institut NeuroMyoGène, UMR CNRS 5310 - INSERM U1217, Université Claude Bernard Lyon 1, Villeurbanne, France., Nowak KJ; Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, Western Australia, Australia. kristen.nowak@health.wa.gov.au.; School of Biomedical Sciences, Faculty of Health and Medical Sciences, The University of Western Australia, Nedlands, Australia. kristen.nowak@health.wa.gov.au.; Office of Population Health Genomics, Public and Aboriginal Health Division, Western Australian Department of Health, East Perth, Western Australia, Australia. kristen.nowak@health.wa.gov.au.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2018 Jul 31; Vol. 8 (1), pp. 11490. Date of Electronic Publication: 2018 Jul 31.
DOI: 10.1038/s41598-018-29437-z
Abstrakt: L-tyrosine supplementation may provide benefit to nemaline myopathy (NM) patients, however previous studies are inconclusive, with no elevation of L-tyrosine levels in blood or tissue reported. We evaluated the ability of L-tyrosine treatments to improve skeletal muscle function in all three published animal models of NM caused by dominant skeletal muscle α-actin (ACTA1) mutations. Highest safe L-tyrosine concentrations were determined for dosing water and feed of wildtype zebrafish and mice respectively. NM TgACTA1 D286G -eGFP zebrafish treated with 10 μM L-tyrosine from 24 hours to 6 days post fertilization displayed no improvement in swimming distance. NM TgACTA1 D286G mice consuming 2% L-tyrosine supplemented feed from preconception had significant elevations in free L-tyrosine levels in sera (57%) and quadriceps muscle (45%) when examined at 6-7 weeks old. However indicators of skeletal muscle integrity (voluntary exercise, bodyweight, rotarod performance) were not improved. Additionally no benefit on the mechanical properties, energy metabolism, or atrophy of skeletal muscles of 6-7 month old TgACTA1 D286G and KIActa1 H40Y mice eventuated from consuming a 2% L-tyrosine supplemented diet for 4 weeks. Therefore this study yields important information on aspects of the clinical utility of L-tyrosine for ACTA1 NM.
Databáze: MEDLINE
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