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Heat shock protein 90 regulates IkappaB kinase complex and NF-kappaB activation in angiotensin II-induced cardiac cell hypertrophy.

Authors: Lee, KH  Jang, Y  Chung, JH 
Citation: Lee KH, etal., Exp Mol Med. 2010 Oct 31;42(10):703-11.
Pubmed: (View Article at PubMed) PMID:20980790
DOI: Full-text: DOI:10.3858/emm.2010.42.10.069

Heat shock protein 90 (HSP90), one of the most abundant proteins in the cardiac cells is essential for cell survival. Previous studies have shown that angiotensin II induces cardiac cell hypertrophy. However, the role of HSP90 in the angiotensin II-induced cardiac hypertrophy is unclear. In this study, we showed that HSP90 regulated angiotensin II-induced hypertrophy via maintenance of the IkappaB kinase (IKK) complex stability in cardiac cells. An HSP90 inhibitor, geldanamycin (GA), significantly suppressed angiotensin II-induced [(3)H]leucine incorporation and atrial natriuretic factor expression in cardiac cells. GA also inhibited the NF-kappaB activation induced by angiotensin II. Importantly, treatment with GA caused a degradation of IKKalpha/beta; on the other hand, a proteasome-specific inhibitor restored the level of IKKalpha/beta. We also found that GA prevented HSP90-IKKs complex induced by angiotensin II in cardiac cells. The small interfering RNA (siRNA)-mediated knockdown of HSP90 expression significantly inhibited angiotensin II-induced cell hypertrophy and NF-kappaB activation. These results suggest that angiotensin II-induced cardiac hypertrophy requires HSP90 that regulates the stability and complex of IKK.

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CRRD Object Information
CRRD ID: 5686397
Created: 2012-01-20
Species: All species
Last Modified: 2012-01-20
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.