Taurine inhibits apoptosis by preventing formation of the Apaf-1/caspase-9 apoptosome.
Cardiomyocyte apoptosis contributes to cell death during myocardial infarction. One of the factors that regulate the degree of apoptosis during ischemia is the amino acid taurine. To study the mechanism underlying the beneficial effect of taurine, we examined the interaction between taurine and mitochondria-mediated apoptosis using a simulated ischemia model with cultured rat neonatal cardiomyocytes sealed in closed flasks. Exposure to medium containing 20 mM taurine reduced the degree of apoptosis following periods of ischemia varying from 24 to 72 h. In the untreated group, simulated ischemia for 24 h led to mitochondrial depolarization accompanied by cytochrome c release. The apoptotic cascade was also activated, as evidenced by the activation of caspase-9 and -3. Taurine treatment had no effect on mitochondrial membrane potential and cytochrome c release; however, it inhibited ischemia-induced cleavage of caspase-9 and -3. Taurine loading also suppressed the formation of the Apaf-1/caspase-9 apoptosome and the interaction of caspase-9 with Apaf-1. These findings demonstrate that taurine effectively prevents myocardial ischemia-induced apoptosis by inhibiting the assembly of the Apaf-1/caspase-9 apoptosome.
Takatani
Tomoka
T
Department of Clinical Evaluation of Medicines and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka Univ., Suita, Osaka 565-0871, Japan.
Takahashi
Kyoko
K
Uozumi
Yoriko
Y
Shikata
Eriko
E
Yamamoto
Yasuhiro
Y
Ito
Takashi
T
Matsuda
Takahisa
T
Schaffer
Stephen W
SW
Fujio
Yasushi
Y
Azuma
Junichi
J
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D053477:Apoptotic Protease-Activating Factor 1; D015153:Blotting, Western; D053453:Caspase 9; D020169:Caspases / Q000187:drug effects*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D020287:In Situ Nick-End Labeling; D007511:Ischemia / Q000188:drug therapy / Q000503:physiopathology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008929:Mitochondria, Heart / Q000187:drug effects / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology*; D011233:Precipitin Tests; D011506:Proteins / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013654:Taurine / Q000494:pharmacology*
C506594:Apaf1 protein, rat; D053477:Apoptotic Protease-Activating Factor 1; D011506:Proteins; D013654:Taurine; C506435:Casp9 protein, rat; D053453:Caspase 9; D020169:Caspases