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Zhao C, Liu S, Yang C, et al. Gambogic acid moderates cardiac responses to chronic hypoxia likely by acting on the proteasome and NF-κB pathway. Am J Cardiovasc Dis. 2013;3(3):135-45
Zhao, C., Liu, S., Yang, C., Li, X., Huang, H., Liu, N., Li, S., Wang, X., & Liu, J. (2013). Gambogic acid moderates cardiac responses to chronic hypoxia likely by acting on the proteasome and NF-κB pathway. American journal of cardiovascular disease, 3(3), 135-45.
Zhao, Canguo, et al. "Gambogic acid moderates cardiac responses to chronic hypoxia likely by acting on the proteasome and NF-κB pathway." American journal of cardiovascular disease vol. 3,3 (2013): 135-45.
Zhao C, Liu S, Yang C, Li X, Huang H, Liu N, Li S, Wang X, Liu J. Gambogic acid moderates cardiac responses to chronic hypoxia likely by acting on the proteasome and NF-κB pathway. Am J Cardiovasc Dis. 2013 Aug 16;3(3):135-45. eCollection 2013. PMID: 23991348; PMCID: PMC3751679.
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Am J Cardiovasc Dis. 2013 Aug 16;3(3):135-45. eCollection 2013.

Gambogic acid moderates cardiac responses to chronic hypoxia likely by acting on the proteasome and NF-κB pathway.

American journal of cardiovascular disease

Canguo Zhao, Shouting Liu, Changshan Yang, Xiaofen Li, Hongbiao Huang, Ningning Liu, Shujue Li, Xuejun Wang, Jinbao Liu

Affiliations

  1. Protein Modification and Degradation Lab, Department of Pathophysiology, Guangzhou Medical University Guangdong 510182, China.

PMID: 23991348 PMCID: PMC3751679

Abstract

Gambogic acid (GA) is the principal active ingredient of gamboges. GA was reported to exert anti-tumor and anti-inflammatory effects both in vitro and in vivo. Previously, we have shown that GA is a more tissue-specific proteasome inhibitor than bortezomib and it is less toxic to peripheral white blood cells compared to bortezomib. Ubiquitous proteasome inhibition was shown by some reports, but not by others, to prevent cardiac remodeling in response to pressure overload by blocking the NF-κB pathway; however, whether GA modulates the development of chronic hypoxia-induced right ventricular hypertrophy has not been investigated yet. Here we report that GA can significantly attenuate right ventricular hypertrophy induced by chronic hypoxia, reduce cardiac fibrosis, and remarkably block the reactivation of bona fide fetal genes in the cardiac tissue. Furthermore, we also investigated the potential molecular targets of GA on right ventricular hypertrophy. The results showed that GA could accumulate the IκB levels associated with decreased proteasomal activity, block the translocation of NF-κB from the cytoplasm to the nucleus, decrease NF-κB DNA-binding activity, and reduce IL-2 levels. In conclusion, GA is capable of preventing the development of chronic hypoxia-induced right ventricular hypertrophy. GA has great potential to be developed into an effective anti-hypertrophy agent.

Keywords: Gambogic acid; NF-κB; chronic hypoxia; right ventricular hypertrophy

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