Hdac2 regulates the cardiac hypertrophic response by modulating Gsk3 beta activity.

Hdac2 regulates the cardiac hypertrophic response by modulating Gsk3 beta activity. Research Abstract Details 

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Hdac2 regulates the cardiac hypertrophic response by modulating Gsk3 beta activity. Abstract Text:

Chinmay M Trivedi,Yang Luo,Zhan Yin,Maozhen Zhang,Wenting Zhu,Tao Wang,Thomas Floss,Martin Goettlicher,Patricia Ruiz Noppinger,Wolfgang Wurst,Victor A Ferrari,Charles S Abrams,Peter J Gruber,Jonathan A Epstein,

In the adult heart, a variety of stresses induce re-expression of a fetal gene program in association with myocyte hypertrophy and heart failure. Here we show that histone deacetylase-2 (Hdac2) regulates expression of many fetal cardiac isoforms. Hdac2 deficiency or chemical histone deacetylase (HDAC) inhibition prevented the re-expression of fetal genes and attenuated cardiac hypertrophy in hearts exposed to hypertrophic stimuli. Resistance to hypertrophy was associated with increased expression of the gene encoding inositol polyphosphate-5-phosphatase f (Inpp5f) resulting in constitutive activation of glycogen synthase kinase 3beta (Gsk3beta) via inactivation of thymoma viral proto-oncogene (Akt) and 3-phosphoinositide-dependent protein kinase-1 (Pdk1). In contrast, Hdac2 transgenic mice had augmented hypertrophy associated with inactivated Gsk3beta. Chemical inhibition of activated Gsk3beta allowed Hdac2-deficient adults to become sensitive to hypertrophic stimulation. These results suggest that Hdac2 is an important molecular target of HDAC inhibitors in the heart and that Hdac2 and Gsk3beta are components of a regulatory pathway providing an attractive therapeutic target for the treatment of cardiac hypertrophy and heart failure.

Hdac2 regulates the cardiac hypertrophic response by modulating Gsk3 beta activity. Publishing Authors By Initials

CM Trivedi,Y Luo,Z Yin,M Zhang,W Zhu,T Wang,T Floss,M Goettlicher,PR Noppinger,W Wurst,VA Ferrari,CS Abrams,PJ Gruber,JA Epstein,

For similar biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research abstracts see: biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research

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Hdac2 regulates the cardiac hypertrophic response by modulating Gsk3 beta activity. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Nature medicine

VOLUME: 13

Page Numbers: 324-31

Journal Abbreviation: Nat. Med.

ISSN: 1078-8956

DAY: 18

MONTH: 02

YEAR: 2007

Hdac2 regulates the cardiac hypertrophic response by modulating Gsk3 beta activity. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9502015

Hdac2 regulates the cardiac hypertrophic response by modulating Gsk3 beta activity. Keywords Mesh Terms:

KEYWORDS: Signal Transduction

MESH TERMS: physiology

Chemical & Substance for Abstract: Hdac2 regulates the cardiac hypertrophic response by modulating Gsk3 beta activity. Information

Substance Name: histone deacetylase-2

Registry Number: EC 3.5.1.-

Grant and Affiliation Information for Hdac2 regulates the cardiac hypertrophic response by modulating Gsk3 beta activity.

AFFILIATION: Department of Cell and Developmental Biology, 1156 Basic Research Building II, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: R01 HL071546

ACRONYM: HL

MEDLINETA: Nat Med

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