Activators of PPARγ antagonize protection of cardiac myocytes by endothelin-1
Activators of PPARγ antagonize protection of cardiac myocytes by endothelin-1
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DOI：
10.1016/j.bbrc.2004.06.147
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发表时间：
2004-08-20
影响因子：
3.1
通讯作者：
Kita, T
中科院分区：
文献类型：
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作者：
Ehara, N;Hasegawa, K;Kita, T
内皮素-1（ET-1）是一种有效的抗心肌细胞凋亡的存活因子。ET-1的这种抗凋亡作用部分通过钙调神经磷酸酶[NFATc]依赖性诱导bcl-2表达介导。由于已报道过氧化物酶体增殖物激活受体-γ（PPARgamma）与NFATc相互作用，我们研究了PPARgamma配体对ET-1在心肌细胞中的抗凋亡作用的影响。在新生大鼠的原代心肌细胞中，给予PPARgamma激活剂（15-脱氧-Delta（12，14）-前列腺素J（2）和曲格列酮）减弱了ET-1的抗凋亡作用。这些激活剂消除了ET-1刺激的bcl-2表达的增加和心脏NFATc与bcl-2 NFAT位点的结合。这些发现表明，PPARgamma的激活剂干扰ET-1在心肌细胞中的抗凋亡作用，并且这种干扰部分地基于NFATc和PPARgamma之间的功能性转录串扰。(C)2004年爱思唯尔公司All rights reserved.
Endothelin-1 (ET-1) is a potent survival factor against myocardial cell apoptosis. This anti-apoptotic effect of ET-I is mediated in part through calcineurin[NFATc-dependent induction of bcl-2 expression. Since it has been reported that peroxisome proliferator-activated receptor-gamma (PPARgamma) interacts with NFATc, we investigated the effects of PPARgamma ligands on anti-apoptotic effects of ET-I in cardiac myocytes. In primary cardiac myocytes from neonatal rats, administration of PPARgamma activators (15-deoxy-Delta(12,14)-prostaglandin J(2), and troglitazone) attenuated the anti-apoptotic effects of ET-1. These activators abolished the ET-I-stimulated increase in bcl-2 expression and in binding of cardiac NFATc to the bcl-2 NFAT site. These findings demonstrate that activators of PPARgamma perturb the anti-apoptotic effects of ET-I in cardiac myocytes and that this perturbation is, in part, based on functional transcriptional cross-talk between NFATc and PPARgamma. (C) 2004 Elsevier Inc. All rights reserved.