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 IκB kinase (IKK) complex stability in cardiac cells. An HSP90 inhibitor, geldanamycin (GA), significantly suppressed angiotensin II-induced [3H]leucine incorporation and atrial natriuretic factor expression in cardiac cells. GA also inhibited the NF-κB activation induced by angiotensin II. Importantly, treatment with GA caused a degradation of IKKα/β; on the other hand, a proteasome-specific inhibitor restored the level of IKKα/β. 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-κB activation. These results suggest that angiotensin II-induced cardiac hypertrophy requires HSP90 that regulates the stability and complex of IKK.
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Molecular Biology
- Clinical Biochemistry