title: Taurine depletion caused by knocking out the taurine transporter gene leads to cardiomyopathy with cardiac atrophy.
abstract: The sulfur-containing beta-amino acid, taurine, is the most abundant free amino acid in cardiac and skeletal muscle. Although its physiological function has not been established, it is thought to play an important role in ion movement, calcium handling, osmoregulation and cytoprotection. To begin examining the physiological function of taurine, we generated taurine transporter- (TauT-) knockout mice (TauTKO), which exhibited a deficiency in myocardial and skeletal muscle taurine content compared with their wild-type littermates. The TauTKO heart underwent ventricular remodeling, characterized by reductions in ventricular wall thickness and cardiac atrophy accompanied with the smaller cardiomyocytes. Associated with the structural changes in the heart was a reduction in cardiac output and increased expression of heart cardiac failure (fetal) marker genes, such as ANP, BNP and beta-MHC. Moreover, ultrastructural damage to the myofilaments and mitochondria was observed. Further, the skeletal muscle of the TauTKO mice also exhibited decreased cell volume, structural defects and a reduction of exercise endurance capacity. Importantly, the expression of Hsp70, ATA2 and S100A4, which are upregulated by osmotic stress, was elevated in both heart and skeletal muscle of the TauTKO mice. Taurine depletion causes cardiomyocyte atrophy, mitochondrial and myofiber damage and cardiac dysfunction, effects likely related to the actions of taurine. Our data suggest that multiple actions of taurine, including osmoregulation, regulation of mitochondrial protein expression and inhibition of apoptosis, collectively ensure proper maintenance of cardiac and skeletal muscular structure and function.
authors.affiliation: Department of Clinical Pharmacology and Pharmacogenomics, Graduate School of Pharmaceutical Sciences, Osaka University, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ito
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kimura
authors.forename: Yoriko
authors.initials: Y
authors.lastname: Uozumi
authors.forename: Mika
authors.initials: M
authors.lastname: Takai
authors.forename: Satoko
authors.initials: S
authors.lastname: Muraoka
authors.forename: Takahisa
authors.initials: T
authors.lastname: Matsuda
authors.forename: Kei
authors.initials: K
authors.lastname: Ueki
authors.forename: Minoru
authors.initials: M
authors.lastname: Yoshiyama
authors.forename: Masahito
authors.initials: M
authors.lastname: Ikawa
authors.forename: Masaru
authors.initials: M
authors.lastname: Okabe
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Schaffer
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Fujio
authors.forename: Junichi
authors.initials: J
authors.lastname: Azuma
mesh_terms: D000818:Animals; D001284:Atrophy; D009202:Cardiomyopathies / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology; D048429:Cell Size; D015536:Down-Regulation; D018390:Gene Targeting; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000172:deficiency* / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000201:enzymology / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000473:pathology / Q000648:ultrastructure; D009206:Myocardium / Q000201:enzymology / Q000473:pathology* / Q000648:ultrastructure; D032383:Myocytes, Cardiac / Q000201:enzymology / Q000473:pathology; D009210:Myofibrils / Q000473:pathology / Q000648:ultrastructure; D020411:Oligonucleotide Array Sequence Analysis; D009929:Organ Size; D009997:Osmotic Pressure; D010805:Physical Conditioning, Animal; D010807:Physical Endurance; D013385:Succinate Dehydrogenase / Q000235:genetics; D013654:Taurine / Q000172:deficiency*; D000099247:Taurine Transporters
chemical_list: D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D013385:Succinate Dehydrogenase; D013654:Taurine; D000099247:Taurine Transporters