Journal
EXPERIMENTAL AND MOLECULAR MEDICINE
Volume 42, Issue 10, Pages 703-711Publisher
KOREAN SOC MED BIOCHEMISTRY MOLECULAR BIOLOGY
DOI: 10.3858/emm.2010.42.10.069
Keywords
angiotensin II; cardiomyopathy, hypertrophic; geldanamycin; HSP90 heat-shock proteins; I kappa B kinase; NF-kappa B
Funding
- Ministry of Education, Science and Technology (MEST)
- Ministry of Knowledge Economy (MKE)
- Ministry of Labor (MOLAB) through Lab of Excellency
- Ministry of Education, Science and Technology [2009-0075206]
- Ministry for Health, Welfare & Family Affairs, Republic of Korea [A085136]
- Yonsei University College of Medicine [8-2009-0190]
- National Research Foundation of Korea [2009-0075206] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Ask authors/readers for more resources
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 la 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-kappa B activation induced by angiotensin II. Importantly, treatment with GA caused a degradation of IKK alpha/beta; on the other hand, a proteasome-specific inhibitor restored the level of IKK alpha/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-kappa B activation. These results suggest that angiotensin II-induced cardiac hypertrophy requires HSP90 that regulates the stability and complex of IKK.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available