title: Taurine deficiency, synthesis and transport in the mdx mouse model for Duchenne Muscular Dystrophy.
abstract: The amino acid taurine is essential for the function of skeletal muscle and administration is proposed as a treatment for Duchenne Muscular Dystrophy (DMD). Taurine homeostasis is dependent on multiple processes including absorption of taurine from food, endogenous synthesis from cysteine and reabsorption in the kidney. This study investigates the cause of reported taurine deficiency in the dystrophic mdx mouse model of DMD. Levels of metabolites (taurine, cysteine, cysteine sulfinate and hypotaurine) and proteins (taurine transporter [TauT], cysteine deoxygenase and cysteine sulfinate dehydrogenase) were quantified in juvenile control C57 and dystrophic mdx mice aged 18 days, 4 and 6 weeks. In C57 mice, taurine content was much higher in both liver and plasma at 18 days, and both cysteine and cysteine deoxygenase were increased. As taurine levels decreased in maturing C57 mice, there was increased transport (reabsorption) of taurine in the kidney and muscle. In mdx mice, taurine and cysteine levels were much lower in liver and plasma at 18 days, and in muscle cysteine was low at 18 days, whereas taurine was lower at 4: these changes were associated with perturbations in taurine transport in liver, kidney and muscle and altered metabolism in liver and kidney. These data suggest that the maintenance of adequate body taurine relies on sufficient dietary intake of taurine and cysteine availability and metabolism, as well as retention of taurine by the kidney. This research indicates dystrophin deficiency not only perturbs taurine metabolism in the muscle but also affects taurine metabolism in the liver and kidney, and supports targeting cysteine and taurine deficiency as a potential therapy for DMD.
authors.affiliation: School of Chemistry and Biochemistry, University of Western Australia, Crawley, WA, Australia; School of Anatomy, Physiology and Human Biology, the University of Western Australia, Perth, WA, Australia. Electronic address: jessica.terrill@uwa.edu.au.
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Terrill
authors.affiliation: School of Anatomy, Physiology and Human Biology, the University of Western Australia, Perth, WA, Australia.
authors.forename: Miranda D
authors.initials: MD
authors.lastname: Grounds
authors.affiliation: School of Chemistry and Biochemistry, University of Western Australia, Crawley, WA, Australia.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Arthur
mesh_terms: D000818:Animals; D001692:Biological Transport; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000031:analogs & derivatives / Q000378:metabolism; D004195:Disease Models, Animal; D016189:Dystrophin / Q000172:deficiency / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009137:Muscular Dystrophy, Animal / Q000097:blood / Q000378:metabolism*; D020388:Muscular Dystrophy, Duchenne / Q000097:blood / Q000378:metabolism*; D013654:Taurine / Q000031:analogs & derivatives / Q000097:blood / Q000172:deficiency / Q000378:metabolism*; D013997:Time Factors
chemical_list: D016189:Dystrophin; D013654:Taurine; C003949:hypotaurine; D003545:Cysteine; C013461:cysteine sulfinic acid
keywords: Cysteine; Duchenne Muscular Dystrophy; Taurine; Taurine synthesis; Taurine transport; mdx mice