Abstract 618: Disruption of Taurine Transporter Gene Results in Abnormal Cardiac Morphology Associated with Impairment of Mitochondrial Ultrastructure and Function in Mice
Background: Taurine, a sulfur-containing β-amino acid, is the most abundant amino acid in cardiac muscle. Accumulating evidences have proposed that taurine plays important roles in ion movement, calcium handling, and regulation of mitochondrial functions in muscles, contributing to tissue protection. However pathophysiological significances remain to be elucidated.
Methods and Results: Taurine transporter-(TauT-) knockout mice (TauTKO) were generated by replacing exon2– 4 with a neomycin resistance gene cassette. KO mice displayed the reduction in taurine content in the hearts (< 0.01 (TauTKO) v.s. 6.7±2.7 (wild) μmol/g wet weight, p<0.001) as well as the other tissues. Histological analyses by hematoxylin-eosin staining revealed that TauTKO hearts exhibited the reduction in wall thickness and the dilation of left ventricles, compared with wild-type littermates. Though cardiac fibrosis was not observed in TauTKO hearts by Masson’s trichrome staining, TauTKO hearts exhibited increased expressions of cardiac failure markers, ANP, BNP and β-MHC, analyzed by northern blot. Transmission electron microscopic examination demonstrated abnormal ultrastructures and collapses of mitochondria in TauTKO hearts. Enzymatic histological staining revealed that succinate dehydrogenase (SDH) activity was remarkably decreased in the hearts of TauTKO compared with wild-type littermates (43±16 % (p<0.05)), indicating the impairment of the capacity of oxidative phospholylation in cardiac mitochondria by taurine depletion.
Conclusion: These results indicate that taurine depletion causes mitochondrial dysfunction in cardiac muscle, and taurine could preserve mitochondrial function, which may result in cardioprotection.