Taurine prevents the ischemia-induced apoptosis in cultured neonatal rat cardiomyocytes through Akt/caspase-9 pathway

被引:95
作者
Takatani, T
Takahashi, K
Uozumi, Y
Matsuda, T
Ito, T
Schaffer, SW
Fujio, Y
Azuma, J [1 ]
机构
[1] Osaka Univ, Grad Sch Pharmaceut Sci, Dept clin Evaluat Med & Therapeut, Osaka, Japan
[2] Univ S Alabama, Sch Med, Dept Pharmacol, Mobile, AL 36688 USA
关键词
taurine; ischemia; apoptosis; Akt; cultured cardiomyocytes;
D O I
10.1016/j.bbrc.2004.02.066
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:484 / 489
页数:6
相关论文
共 35 条
[1]  
Aikawa R, 2000, CIRCULATION, V102, P2873
[2]   Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT [J].
Baldanzi, G ;
Filigheddu, N ;
Cutrupi, S ;
Catapano, F ;
Bonissoni, S ;
Fubini, A ;
Malan, D ;
Baj, G ;
Granata, R ;
Broglio, F ;
Papotti, M ;
Surico, N ;
Bussolino, F ;
Isgaard, J ;
Deghenghi, R ;
Sinigaglia, F ;
Prat, M ;
Muccioli, G ;
Ghigo, E ;
Graziani, A .
JOURNAL OF CELL BIOLOGY, 2002, 159 (06) :1029-1037
[3]   The mitochondrial apoptotic pathway is activated by serum and glucose deprivation in cardiac myocytes [J].
Bialik, S ;
Cryns, VL ;
Drincic, A ;
Miyata, S ;
Wollowick, AL ;
Srinivasan, A ;
Kitsis, RN .
CIRCULATION RESEARCH, 1999, 85 (05) :403-414
[4]   Release of mitochondrial cytochrome c and activation of cytosolic caspases induced by myocardial ischaemia [J].
Borutaite, V ;
Budriunaite, A ;
Morkuniene, R ;
Brown, GC .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2001, 1537 (02) :101-109
[5]  
Campana WM, 1999, J NEUROSCI RES, V57, P332
[6]   Regulation of cell death protease caspase-9 by phosphorylation [J].
Cardone, MH ;
Roy, N ;
Stennicke, HR ;
Salvesen, GS ;
Franke, TF ;
Stanbridge, E ;
Frisch, S ;
Reed, JC .
SCIENCE, 1998, 282 (5392) :1318-1321
[7]   Calcium regulates the PI3K-Akt pathway in stretched osteoblasts [J].
Danciu, TE ;
Adam, RM ;
Naruse, K ;
Freeman, MR ;
Hauschka, PV .
FEBS LETTERS, 2003, 536 (1-3) :193-197
[8]   Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery [J].
Datta, SR ;
Dudek, H ;
Tao, X ;
Masters, S ;
Fu, HA ;
Gotoh, Y ;
Greenberg, ME .
CELL, 1997, 91 (02) :231-241
[9]   Taurine prevents high-glucose-induced human vascular endothelial cell apoptosis [J].
Di Wu, Q ;
Wang, JH ;
Fennessy, F ;
Redmond, HP ;
Bouchier-Hayes, D .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 1999, 277 (06) :C1229-C1238
[10]   Regulation of neuronal survival by the serine-threonine protein kinase Akt [J].
Dudek, H ;
Datta, SR ;
Franke, TF ;
Birnbaum, MJ ;
Yao, RJ ;
Cooper, GM ;
Segal, RA ;
Kaplan, DR ;
Greenberg, ME .
SCIENCE, 1997, 275 (5300) :661-665