Taurine depletion caused by knocking out the taurine transporter gene leads to cardiomyopathy with cardiac atrophy

被引:177
作者
Ito, Takashi [1 ]
Kimura, Yasushi [1 ]
Uozumi, Yoriko [1 ]
Takai, Mika [1 ]
Muraoka, Satoko [1 ]
Matsuda, Takahisa [1 ]
Ueki, Kei [5 ]
Yoshiyama, Minoru [4 ]
Ikawa, Masahito [3 ]
Okabe, Masara [3 ]
Schaffer, Stephen W. [2 ]
Fujio, Yasushi [1 ]
Azuma, Junichi [1 ]
机构
[1] Osaka Univ, Grad Sch Pharmaceut Sci, Dept Clin Pharmacol & Pharmacogenom, Suita, Osaka 5650871, Japan
[2] Univ S Alabama, Coll Med, Dept Pharmacol, Mobile, AL 36688 USA
[3] Osaka Univ, Microbial Dis Res Inst, Suita, Osaka 565, Japan
[4] Osaka City Univ, Sch Med, Dept Internal Med & Cardiol, Osaka, Japan
[5] Japan Clin Labs Inc, Bioassay Div, Osaka, Japan
关键词
taurine; taurine transporter; heart; cardiomyopathy; atrophy; transgenic mice; mitochondrial defect; cell volume; osmoregulation;
D O I
10.1016/j.yjmcc.2008.03.001
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. (C) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:927 / 937
页数:11
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