Modulation of the caveolin-3 localization to caveolae and STAT3 to mitochondria by catecholamine-induced cardiac hypertrophy in H9c2 cardiomyoblasts
Modulation of the caveolin-3 localization to caveolae and STAT3 to mitochondria by catecholamine-induced cardiac hypertrophy in H9c2 cardiomyoblasts
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DOI：
10.3858/emm.2009.41.4.025
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发表时间：
2009-04-30
影响因子：
12.8
通讯作者：
Pak, Yunbae
中科院分区：
文献类型：
--
作者：
Jeong, Kyuho;Kwon, Hayeong;Pak, Yunbae
研究苯肾上腺素(PE)和异丙肾上腺素(ISO)诱导的心肌肥厚对H9c2成心肌细胞小窝蛋白-3和STAT3亚细胞定位和表达的影响。儿茶酚胺诱导的肥大使小窝蛋白3在质膜上的定位减弱，在质膜上的小窝定位减少24.3%。在PE和ISO诱导的肥大细胞中，STAT3和磷酸化STAT3表达上调，但维拉帕米和环孢菌素A协同降低STAT3和磷酸化STAT3水平。STAT3在胞核的表达和激活均因肥大而增加。免疫荧光分析显示，儿茶酚胺诱导的肥大促进了pY705-STAT3的核定位。有趣的是，儿茶酚胺诱导的肥大显著降低了线粒体中pS727-STAT3的磷酸化。此外，线粒体复合体II和III在肥大细胞中的表达显著下调。我们的数据提示，STAT3的核和线粒体激活的改变以及小凹-3的小窝定位与儿茶酚胺诱导的心肌肥厚的发生有关。
We investigated the effect of phenylephrine (PE)- and isoproterenol (ISO)-induced cardiac hypertrophy on subcellular localization and expression of caveolin-3 and STAT3 in H9c2 cardiomyoblast cells. Caveolin-3 localization to plasma membrane was attenuated and localization of caveolin-3 to caveolae in the plasma membrane was 24.3% reduced by the catecholamine-induced hypertrophy. STAT3 and phospho-STAT3 were up-regulated but verapamill and cyclosporin A synergistically decreased the STAT3 and phospho-STAT3 levels in PE- and ISO-induced hypertrophic cells. Both expression and activation of STAT3 were increased in the nucleus by the hypertrophy. Immunofluorescence analysis revealed that the catecholamine-induced hypertrophy promoted nuclear localization of pY705-STAT3. Of interest, phosphorylation of pS727-STAT3 in mitochondria was significantly reduced by catecholamine-induced hypertrophy. In addition, mitochondrial complexes II and III were greatly down-regulated in the hypertrophic cells. Our data suggest that the alterations in nuclear and mitochondrial activation of STAT3 and caveolae localization of caveolin-3 are related to the development of the catecholamine-induced cardiac hypertrophy.