Activation of peroxisome proliferator-activated receptor gamma inhibits endothelin-1-induced cardiac hypertrophy via the calcineurin/NFAT signaling pathway
Activation of peroxisome proliferator-activated receptor gamma inhibits endothelin-1-induced cardiac hypertrophy via the calcineurin/NFAT signaling pathway
复制标题
过氧化物酶体增殖物激活受体γ的激活通过钙调神经磷酸酶/NFAT信号通路抑制内皮素-1诱导的心脏肥大
DOI：
10.1007/s11010-008-9848-8
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发表时间：
2008-10-01
影响因子：
4.3
通讯作者：
Liu, Peiqing
中科院分区：
文献类型：
--
作者：
Bao, Yingxia;Li, Ruifang;Liu, Peiqing
过氧化物酶体增殖物激活受体γ（PPAR-gamma）已被描述为心脏肥大的负调节因子。更好地了解PPAR-gamma和心脏肥大可能有助于开发新的治疗策略，通过模拟自然首选机制来治疗与心脏肥大相关的心脏疾病。在本研究中，我们研究了PPAR-gamma和钙调神经磷酸酶/活化T细胞核因子（NFAT）在内皮素-1（ET-1）诱导的新生大鼠心肌细胞肥大中的相互作用。结果表明，用PPAR-gamma配体罗格列酮处理培养的心肌细胞，抑制了ET-1诱导的蛋白质合成、表面积、钙调磷酸酶酶活性和蛋白质表达的增加。罗格列酮的应用和PPAR-gamma的过度表达都抑制了NFATc 4的核转位。此外，免疫共沉淀研究表明，罗格列酮增强了PPAR-gamma和钙调神经磷酸酶/NFAT之间的关联。这些结果表明，ET-1诱导的心脏肥大抑制激活的PPAR-gamma，这是至少部分地由于之间的串扰PPAR-gamma和钙调神经磷酸酶/NFAT。
Peroxisome proliferator-activated receptor gamma (PPAR-gamma) has been described as a negative regulator of cardiac hypertrophy. A better understanding of PPAR-gamma and cardiac hypertrophy may facilitate the development of novel therapeutic strategies to treat heart diseases related to cardiac hypertrophy by mimicking the naturally preferred mechanisms. In the present study, we investigated the interaction between PPAR-gamma and calcineurin/nuclear factor of activated T-cells (NFAT) in endothelin-1 (ET-1)-induced hypertrophy of neonatal rat cardiac myocytes. The results suggest that the treatment of cultured cardiac myocytes with a PPAR-gamma ligand, rosiglitazone, inhibited the ET-1-induced increase in protein synthesis, surface area, calcineurin enzymatic activity, and protein expression. Both the application of rosiglitazone and overexpression of the PPAR-gamma inhibited the nuclear translocation of NFATc4. Moreover, co-immunoprecipitation studies showed that rosiglitazone enhanced the association between PPAR-gamma and calcineurin/NFAT. These results suggest that ET-1-induced cardiac hypertrophy is inhibited by activation of PPAR-gamma, which is at least partly due to cross-talk between PPAR-gamma and calcineurin/NFAT.