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Nat Commun. 2015 Apr 14;6:6656. doi: 10.1038/ncomms7656.

Honokiol blocks and reverses cardiac hypertrophy in mice by activating mitochondrial Sirt3.

Author information

1
Departments of Surgery, University of Chicago, Chicago, Illinois, USA.
2
Departments of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois, USA.
3
Departments of Medicine, University of Chicago, Chicago, Illinois 60637, USA.
4
Department of Dermatology, Atlanta Veterans Administration Health Center, Atlanta, Georgia, USA.
5
Department of Biochemistry and Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
6
Department of Radiation Oncology, Northwestern University, Chicago, Illinois 60611, USA.

Abstract

Honokiol (HKL) is a natural biphenolic compound derived from the bark of magnolia trees with anti-inflammatory, anti-oxidative, anti-tumour and neuroprotective properties. Here we show that HKL blocks agonist-induced and pressure overload-mediated, cardiac hypertrophic responses, and ameliorates pre-existing cardiac hypertrophy, in mice. Our data suggest that the anti-hypertrophic effects of HKL depend on activation of the deacetylase Sirt3. We demonstrate that HKL is present in mitochondria, enhances Sirt3 expression nearly twofold and suggest that HKL may bind to Sirt3 to further increase its activity. Increased Sirt3 activity is associated with reduced acetylation of mitochondrial Sirt3 substrates, MnSOD and oligomycin-sensitivity conferring protein (OSCP). HKL-treatment increases mitochondrial rate of oxygen consumption and reduces ROS synthesis in wild type, but not in Sirt3-KO cells. Moreover, HKL-treatment blocks cardiac fibroblast proliferation and differentiation to myofibroblasts in a Sirt3-dependent manner. These results suggest that HKL is a pharmacological activator of Sirt3 capable of blocking, and even reversing, the cardiac hypertrophic response.

PMID:
25871545
PMCID:
PMC4441304
DOI:
10.1038/ncomms7656
[Indexed for MEDLINE]
Free PMC Article

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