Abstract 299: Taurine Is Essential For Cellular Osmoregulation In The Heart

Abstract

[Background] Taurine, a sulfur-containing β-amino acid, is the most abundant free amino acid in mammalian tissues, especially cardiac muscles. Taurine is reported to be beneficial for patients with congestive heart failure; however, it remains to be fully elucidated how taurine exhibits its cardioprotective effects. To address the molecular mechanisms for its cardioprotective roles, we investigated functional and morphological phenotypes in mice lacking taurine transporter gene (TauTKO). [Methods and Results] Taurine content was dramatically decreased in hearts of TauTKO mice. Echocardiographic analysis revealed that TauTKO hearts showed impaired cardiac output (Fractional shortening (%): 32.3 ± 3.6 (wild) vs 22.5 ± 2.2 (TauTKO), p <0.05). Histological analyses showed ventricular wall thickness was thinner in TauTKO mice than wild-type littermates, which was concomitant with decreased myocyte sizes in TauTKO ventricles (211.2 ± 5.0 v.s. 153.6 ± 5.2 μm 2 , p <0.01). Furthermore, to analyze the changes in gene expressions in TauTKO hearts, we performed microarray analyses using total RNA from hearts muscles. Importantly, hypertonicity-inducible genes, such as hspa1a/b (heat shock protein 70), slc38a2 (amino acid transporter-2) and s100a4 (S100 calcium binding protein A4), were upregulated more than 1.7-fold in cardiac muscles of TauTKO mice, compared with control. The inductions of these genes were verified by real time quantitative RT-PCR (hspa1a/b; 4.8 ± 1.3 (fold), slc38a2; 3.3 ± 0.5, s100a4; 1.7 ± 0.13), suggesting that hypertonicity-inducible signaling pathways are activated in TauTKO hearts. Interestingly, the upregulation of these hypertonicity-inducible genes was also observed in skeletal muscles that exhibited decreased cell size in TauTKO mice, proposing the possibility that taurine-mediated osmoregulatory signals are widely utilized in various kinds of cell lineages as a novel cytoprotective system. [Conclusion] Intracellular taurine depletion leads to cellular osmotic impairment and results in cardiac dysfunction, accompanied by myocyte size decrease. Taurine transporter could be essential for the maintenance of intracellular osmotic homeostasis in cardiac myocytes.