期刊
EXPERIMENTAL AND MOLECULAR MEDICINE
卷 41, 期 4, 页码 226-235出版社
NATURE PUBLISHING GROUP
DOI: 10.3858/emm.2009.41.4.025
关键词
cardiomegaly; caveolae; caveolin-3; cell nucleus; heart; isoproterenol; mitochondria; phenylephrine; STAT3 transcription factor
资金
- Research Promotion Program [RPP-2006-020]
- Gyeongsang National University
- MOST/KOSEF
- BK21 Program
- Ministry of Education and Human Resources Development, Korea
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.
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