title: Suberoylanilide Hydroxamic Acid Restores Estrogen Reduced-cTnI Expression in Neonatal Hearts of Mice.
abstract: Diastolic cardiac dysfunction can be caused by abnormality in cTnI expression during cardiogenesis. In this study, we investigated the effects of estrogen on the abnormal expression of cTnI in the hearts of neonatal mice and its potential epigenetic mechanisms. We then evaluated suberoylanilide hydroxamic acid (SAHA), a HDAC inhibitor, as a new target treatment of diastolic cardiac dysfunction. Postnatal day 0.5 C57BL/6 mice were injected with estrogen for 1 week, then the hearts of 7-day-old neonatal mice were retrieved for examination. The activities of HDAC and HAT were assayed by colorimetry, and the interaction of cTnI with HDAC5 in mice hearts were examined using chromatin immunoprecipitation assays. The expression of cTnI was tested by quantitative real-time RT-PCR and Western blot. Estrogen treated groups displayed a significantly increased HDAC activity in the hearts of neonatal mice while HAT activity remained unchanged. Additionally, HDAC5 was higher at the cTnI promoter, as compared to the saline treated control groups. The acetylation of histone H3K9ac on cTnI promoter significantly decreased in the hearts of neonatal mice treated with estrogen, and the expression of cTnI at transcriptional and protein levels also decreased. SAHA was shown to increase the acetylation of histone H3K9ac and upregulate the expression of cTnI. The data demonstrated that SAHA can correct cTnI expression abnormality caused by estrogen through inhibiting the binding of HDAC5 to the promoter of cTnI. J. Cell. Biochem. 117: 2377-2384, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Pediatrics, Affiliated Hospital of Zunyi Medical College, Guizhou, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Peng
authors.affiliation: Department of Physiology, Zunyi Medical College, Guizhou, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Pediatrics, Affiliated Hospital of Zunyi Medical College, Guizhou, China.
authors.forename: Qianlu
authors.initials: Q
authors.lastname: Xing
authors.affiliation: Heart Center, Children's Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Huichao
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Biomedical Science, Charlie E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida.
authors.forename: Xupei
authors.initials: X
authors.lastname: Huang
mesh_terms: D000107:Acetylation; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D004967:Estrogens / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019210:Troponin I / Q000378:metabolism*; D000077337:Vorinostat
chemical_list: D004967:Estrogens; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D012333:RNA, Messenger; D019210:Troponin I; D000077337:Vorinostat; C404500:HDAC5 protein, human; D006655:Histone Deacetylases
keywords: ESTROGEN; HISTONE ACETYLATION; SAHA; cTnI