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
[31]   Taurine renders the cell resistant to ischemia-induced injury in cultured neonatal rat cardiomyocytes [J].
Takahashi, K ;
Ohyabu, Y ;
Takahashi, K ;
Solodushko, V ;
Takatani, T ;
Itoh, T ;
Schaffer, SW ;
Azuma, J .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 2003, 41 (05) :726-733
[32]   Cellular characterization of an in-vitro cell culture model of seal-induced cardiac ischaemia [J].
Takahashi, K ;
Ohyabu, Y ;
Schaffer, SW ;
Azuma, J .
JOURNAL OF PHARMACY AND PHARMACOLOGY, 2001, 53 (03) :379-386
[33]   Hyperosmolality activates Akt and regulates apoptosis in renal tubular cells [J].
Terada, Y ;
Inoshita, S ;
Hanada, S ;
Shimamura, H ;
Kuwahara, M ;
Ogawa, W ;
Kasuga, M ;
Sasaki, S ;
Marumo, F .
KIDNEY INTERNATIONAL, 2001, 60 (02) :553-567
[34]  
Verzola D, 2002, J INVEST MED, V50, P443, DOI 10.1136/jim-50-06-04
[35]   Reperfusion-activated Akt kinase prevents apoptosis in transgenic mouse hearts overexpressing insulin-like growth factor-1 [J].
Yamashita, K ;
Kajstura, J ;
Discher, DJ ;
Wasserlauf, BJ ;
Bishopric, NH ;
Anversa, P ;
Webster, KA .
CIRCULATION RESEARCH, 2001, 88 (06) :609-614