Taurine prevents the ischemia-induced apoptosis in cultured neonatal rat cardiomyocytes through Akt/caspase-9 pathway.
Activated Akt kinase has been proposed as a central role in suppressing apoptosis by modulating the activities of Bcl-2 family proteins and/or caspase-9. To study the mechanism underlying the anti-apoptotic effect of taurine, the interaction between taurine and Akt/caspase-9 pathway was examined using a simulated ischemia model with cultured rat neonatal cardiomyocytes sealed in closed flasks. Taurine (20mM) treatment attenuated simulated ischemia-induced decline in the activity of Akt. Although taurine treatment had no effect on the expression of Bcl-2 in mitochondria and the level of cytosolic cytochrome c, it inhibited ischemia-induced cleavage of caspases 9 and 3. Moreover, adenovirus transfer of the dominant negative form of Akt objected taurine-mediated anti-apoptotic effects, cancelling the suppression of caspase-9 and caspase-3 activities by taurine. These findings provide the first evidence that taurine inhibits ischemia-induced apoptosis in cardiac myocytes with the increase in Akt activities, by inactivating caspase-9.
Takatani
Tomoka
T
Department of Clinical Evaluation of Medicines and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
Takahashi
Kyoko
K
Uozumi
Yoriko
Y
Matsuda
Takahisa
T
Ito
Takashi
T
Schaffer
Stephen W
SW
Fujio
Yasushi
Y
Azuma
Junichi
J
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D002478:Cells, Cultured; D019610:Cytoprotection; D017202:Myocardial Ischemia / Q000517:prevention & control; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013654:Taurine / Q000494:pharmacology*
D011518:Proto-Oncogene Proteins; D013654:Taurine; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; C506435:Casp9 protein, rat; D053453:Caspase 9; D020169:Caspases