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.