title: Curcumin-mediated cardiac defects in mouse is associated with a reduced histone H3 acetylation and reduced expression of cardiac transcription factors.
abstract: Histone acetylation plays an important role in heart development. However, the mechanism(s) remains unclear. This study was designed to evaluate the effect of curcumin-caused histone hypo-acetylation on the development of mouse embryonic heart and the expression of cardiac transcription factors in vivo. The results showed that curcumin treatment significantly decreased histone acetylase activity and histone acetylation level in mouse embryonic heart. In curcumin-treated mice, the hearts on E11.5 were smaller with thinner ventricular wall and a delayed development of trabeculae and ventricular septum compared with the controls. The ventricular septum was complete on E14.5; however, the ventricular wall and septum were thinner with fewer trabeculae than those in the controls. On E17.5, the cardiac structure appeared normal, but the ventricular wall and septum were thinner. The expression of GATA4, Nkx2.5 and Mef2c in the heart on E11.5 and E14.5 was decreased significantly as compared to the controls. There was no significant difference in Mef2c expression on E17.5 between curcumin-treated group and the controls, while GATA4 and Nkx2.5 expression remained significantly reduced. These results indicate that inhibition of histone acetylation by curcumin can reduce the expression of the cardiac transcription factors resulting in an abnormal heart development in mice.
authors: Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics, Committee of Science and Technology in Chongqing, Heart Centre, Children's Hospital of Chongqing Medical University, Chongqing, 400014, People's Republic of China, cathy8224@163.com.
authors: Huichao
authors: H
authors: Sun
authors: Jing
authors: J
authors: Zhu
authors: Tiewei
authors: T
authors: Lu
authors: Xupei
authors: X
authors: Huang
authors: Jie
authors: J
authors: Tian
mesh_terms: D000107:Acetylation; D000818:Animals; D003474:Curcumin / Q000633:toxicity*; D015536:Down-Regulation; D050991:GATA4 Transcription Factor / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D006321:Heart / Q000187:drug effects* / Q000196:embryology; D006330:Heart Defects, Congenital / Q000139:chemically induced* / Q000196:embryology / Q000201:enzymology; D006657:Histones / Q000378:metabolism*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000378:metabolism; D008239:Lysine; D064326:MEF2 Transcription Factors / Q000378:metabolism; D008813:Mice, Inbred ICR; D009206:Myocardium / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D050880:p300-CBP Transcription Factors / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
chemical_list: D003474:Curcumin; D050991:GATA4 Transcription Factor; D006657:Histones; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; D008239:Lysine; D064326:MEF2 Transcription Factors; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C484171:Gata4 protein, mouse; C578041:Mef2c protein, mouse; C484469:Nkx2-5 protein, mouse