Cardiac and skeletal muscle abnormality in taurine transporter-knockout mice

Ito, Takashi; Oishi, Shohei; Takai, Mika; Kawakami, Yasushi; Uozumi, Yoriko; Fujio, Yasushi; Schaffer, Stephen W.; Azuma, Junichi

doi:10.1186/1423-0127-17-s1-s20

Cited by 80 publications

(68 citation statements)

References 26 publications

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“…considered to be present in skeletal muscles and kidneys (16), and it was suggested that taurine was produced elsewhere and transported to these tissues (21,22). In this study, the expression and biochemical activity of GADL1 in muscles suggested that muscle taurine might be produced in situ.…”

Section: Discussionmentioning

confidence: 58%

Role of Glutamate Decarboxylase-like Protein 1 (GADL1) in Taurine Biosynthesis

Liu

Ding

et al. 2012

Journal of Biological Chemistry

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Background:The biochemical activities and tissue distribution of GADL1 have remained unknown. Results: GADL1 is expressed in muscles and kidneys; it catalyzes decarboxylation of aspartate, cysteine sulfinic acid, and cysteic acid to produce ␤-alanine, hypotaurine, and taurine. Conclusion: GADL1 has aspartate 1-decarboxylase and cysteine sulfinic acid decarboxylase activities. Significance: GADL1 could potentially participate in mammalian taurine biosynthesis.

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Section: Discussionmentioning

confidence: 58%

Role of Glutamate Decarboxylase-like Protein 1 (GADL1) in Taurine Biosynthesis

Liu

Ding

et al. 2012

Journal of Biological Chemistry

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“…org) and SMIT mRNA in the human skeletal muscle are low 16,17 and we could not detect the corresponding protein in normal muscle samples. However, TauT knockout mice suffer from muscle fiber atrophy and necrosis and reduced exercise endurance, 18,19 which implies that these factors could still be crucial factors for muscle recovery after damage. It has been observed that NFAT5 levels increase in the regenerating fibers of mouse tibial muscle following muscle tissue injury.…”

Section: Discussionmentioning

confidence: 99%

Activation of osmolyte pathways in inflammatory myopathy and Duchenne muscular dystrophy points to osmoregulation as a contributing pathogenic mechanism

Paepe

Martin

Herbelet

et al. 2016

Laboratory Investigation

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Alongside well-known nuclear factor κB (NFκB) and its associated cytokine networks, nuclear factor of activated T cells 5 (NFAT5), the master regulator of cellular osmoprotective programs, comes forward as an inflammatory regulator. To gain insight into its yet unexplored role in muscle disease, we studied the expression of NFAT5 target proteins involved in osmolyte accumulation: aldose reductase (AR), taurine transporter (TauT), and sodium myo-inositol co-transporter (SMIT). We analyzed idiopathic inflammatory myopathy and Duchenne muscular dystrophy muscle biopsies and myotubes in culture, using immunohistochemistry, immunofluorescence, and western blotting. We report that the level of constitutive AR was upregulated in patients, most strongly so in Duchenne muscular dystrophy. TauT and SMIT expression levels were induced in patients' muscle fibers, mostly representing regenerating and atrophic fibers. In dermatomyositis, strong staining for AR, TauT, and SMIT in atrophic perifascicular fibers was accompanied by staining for other molecular NFAT5 targets, including chaperones, chemokines, and inducible nitric oxide synthase. In these fibers, NFAT5 and NFκB p65 staining coincided, linking both transcription factors with this important pathogenic hallmark. In sporadic inclusion body myositis, SMIT localized to inclusions inside muscle fibers. In addition, SMIT was expressed by a substantial subset of muscle-infiltrating macrophages and T cells in patient biopsies. Our results indicate that osmolyte pathways may contribute to normal muscle functioning, and that activation of AR, TauT, and SMIT in muscle inflammation possibly contributes to the tissue's failing program of damage control.

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“…Deletion of exon 1 of the TauT gene results in a striking (98%) decrease in heart and skeletal muscle taurine levels, with severely impaired skeletal muscle function and exercise capacity (Warskulat et al, 2004). TauT knockout mice also display severe abnormalities in muscle structure including decreased myofibre cross sectional area, myofilament fragmentation, and lipid droplets within the myofibre (Ito et al, 2008(Ito et al, , 2010.…”

Section: Introductionmentioning

confidence: 97%

“…1. Maintenance of the intracellular taurine pool depends on active uptake from the extracellular space by the high affinity, low capacity, Na + dependent transporter, TauT (Ito et al, 2010), and taurine is released from cells via volume insensitive and volume sensitive leak pathways (Lambert et al, 2014). The liver is responsible for export of a substantial proportion of the taurine body pool into the plasma, and absorption of taurine from the diet in the liver by hepatocytes requires TauT.…”

Section: Introductionmentioning

confidence: 99%

Taurine deficiency, synthesis and transport in the mdx mouse model for Duchenne Muscular Dystrophy

Terrill

Grounds

Arthur

2015

The International Journal of Biochemistry & Cell Biology

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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.

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Cardiac and skeletal muscle abnormality in taurine transporter-knockout mice

Cited by 80 publications

References 26 publications

Role of Glutamate Decarboxylase-like Protein 1 (GADL1) in Taurine Biosynthesis

Role of Glutamate Decarboxylase-like Protein 1 (GADL1) in Taurine Biosynthesis

Activation of osmolyte pathways in inflammatory myopathy and Duchenne muscular dystrophy points to osmoregulation as a contributing pathogenic mechanism

Taurine deficiency, synthesis and transport in the mdx mouse model for Duchenne Muscular Dystrophy

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