Taurine renders the cell resistant to ischemia-induced injury in cultured neonatal rat cardiomyocytes.
Taurine is found in very high concentration in the mammalian heart. Because chronic myocardial taurine loss produces myocardial injury, the effects of taurine supplementation on ischemia-induced necrosis and apoptosis were examined using a cardiomyocyte model of simulated ischemia. Neonatal rat heart cells were cultured for 24-72 h in a sealed flask, a condition that leads to simulated ischemia characterized by a decrease in the pH and oxygen content of the medium and a catabolite accumulation. The consequences of altered medium taurine on cellular apoptosis and necrosis were then evaluated. Exposure of cardiomyocytes to medium containing high extracellular concentrations of taurine (20 mM) significantly elevated intracellular taurine levels, reduced p53 content, and enhanced cellular Bcl-2 content. In the absence of taurine treatment, simulated ischemia led to cellular release of creatine phosphokinase (CPK), morphologic degeneration, and beating cessation by 24-72 h. Based on DNA ladder analysis and the Hoechst 33258 staining pattern, a significant number of cells placed in sealed flasks underwent apoptosis. CPK was lost from some of the cells during simulated ischemia. In contrast to the untreated ischemic cells, the cells that were incubated in medium supplemented with taurine exhibited significantly less ischemia-induced necrosis and apoptosis. The data suggest that taurine renders the cell resistant to ischemia-induced necrosis and apoptosis. The beneficial effects of taurine may be related to the elevation in cellular Bcl-2 content.
Takahashi
Kyoko
K
Department of Clinical Evaluation of Medicines and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
Ohyabu
Yuko
Y
Takahashi
Koichi
K
Solodushko
Viktoriya
V
Takatani
Tomoka
T
Itoh
Takashi
T
Schaffer
Stephen W
SW
Azuma
Junichi
J
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D017202:Myocardial Ischemia / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009336:Necrosis; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013654:Taurine / Q000378:metabolism / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein
D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D013654:Taurine