Beneficial Effect of Taurine Treatment Against Doxorubicin-Induced Cardiotoxicity in Mice
Though the administration of taurine is clinically efficacious against heart failure, the mechanism underlying its cardioprotection remains to be established. To provide information on the mechanism, we examined the effects of taurine on doxorubicin (DOX)-induced cardiotoxicity, with an emphasis on ROS generation and cardiac gene inhibition. Oral administration of taurine (3% w/v in tap water) dramatically reduced the mortality rate in both the acute or sub-acute toxic models of DOX toxicity. It was shown that taurine prevented DOX-induced oxidative stress as determined from cardiac glutathione content. Interestingly, Northern blot analysis revealed that DOX altered cardiac gene expression, including that of α-myosin heavy chain, ventricular myosin light chain-2 isoform and brain natriuretic peptide, an effect partially ameliorated by taurine treatment. In conclusion, taurine suppresses ROS generation and regulates gene expression in the DOX treated heart.
KeywordsReactive Oxygen Species Generation Brain Natriuretic Peptide Myosin Heavy Chain Cardiac Gene Expression Taurine Treatment
Unable to display preview. Download preview PDF.
- Cunningham C, Tipton KF, Dixon HB (1998) Conversion of taurine into N-chlorotaurine (taurine chloramine) and sulphoacetaldehyde in response to oxidative stress. Biochem J 330(Pt 2): 939–945Google Scholar
- Ito T, Fujio Y, Hirata M, Takatani T, Matsuda T, Muraoka S, Takahashi K, Azuma J (2004) Expression of taurine transporter is regulated through the TonE (tonicity-responsive element)/TonEBP (TonE-binding protein) pathway and contributes to cytoprotection in HepG2 cells. Biochem J 382:177–182PubMedCrossRefGoogle Scholar
- Kunisada K, Negoro S, Tone E, Funamoto M, Osugi T, Yamada S, Okabe M, Kishimoto T, Yamauchi-Takihara K (2000) Signal transducer and activator of transcription 3 in the heart transduces not only a hypertrophic sig-nal but a protective signal against doxorubicin-induced cardiomyopathy. Proc Natl Acad Sci USA 97:315–319PubMedCrossRefGoogle Scholar
- Nakaoka Y, Nishida K, Fujio Y, Izumi M, Terai K, Oshima Y, Sugiyama S, Matsuda S, Koyasu S, Yamauchi-Takihara K, Hirano T, Kawase I, Hirota H (2003) Activation of gp130 transduces hypertrophic signal through interaction of scaffolding/docking protein Gab1 with tyrosine phosphatase SHP2 in cardiomyocytes. Circ Res 93:221–229PubMedCrossRefGoogle Scholar
- Toko H, Zhu W, Takimoto E, Shiojima I, Hiroi Y, Zou Y, Oka T, Aka-zawa H, Mizukami M, Sakamoto M, Terasaki F, Kitaura Y, Takano H, Nagai T, Nagai R, Komuro I (2002) Csx/Nkx2-5 is required for homeosta-sis and survival of cardiac myocytes in the adult heart. J Biol Chem 277:24735–24743PubMedCrossRefGoogle Scholar