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Background: Prenatal alcohol exposure may cause cardiac development defects, however, the underlying mechanisms are not yet clear. In the present study we have investigated the roles of histone modification by curcumin on alcohol induced fetal cardiac abnormalities during the development. Methods and results: Q-PCR and Western blot results showed that alcohol exposure increased gene and active forms of caspase-3 and caspase-8, while decreased gene and protein of bcl-2. ChIP assay results showed that, alcohol exposure increased the acetylation of histone H3K9 near the promoter region of caspase-3 and caspase-8, and decreased the acetylation of histone H3K9 near the promoter region of bcl-2. TUNEL assay data revealed that alcohol exposure increased the apoptosis levels in the embryonic hearts. In vitro experiments demonstrated that curcumin treatment could reverse the up-regulation of active forms of caspase-3 and caspase-8, and down-regulation of bcl-2 induced by alcohol treatment. In addition, curcumin also corrected the high level of histone H3K9 acetylation induced by alcohol. Moreover, the high apoptosis level induced by alcohol was reversed after curcumin treatment in cardiac cells. Conclusions: These findings indicate that histone modification may play an important role in mediating alcohol induced fetal cardiac apoptosis, possibly through the up-regulation of H3K9 acetylation near the promoter regions of apoptotic genes. Curcumin treatment may correct alcohol-mediated fetal cardiac apoptosis, suggesting that curcumin may play a protective role against alcohol abuse caused cardiac damage during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Recurrent convulsions can cause irreversible astrocyte death, impede neuron regeneration, and further aggravate brain damage. MicroRNAs have been revealed as players in the progression of numerous diseases including cancer and Alzheimer's disease. Particularly, microRNA has been found linked to seizure-induced neuronal death. In this study, a rat model of recurrent convulsions induced by flurothyl treatments was utilised to assess the alterations of microRNA expressions in hippocampus tissues. We also applied an in vitro model in which primary astrocytes were exposed to kainic acid to verify the targets of miR-34b-5p identified in the animal model.Results: We discovered that miR-34b-5p, a member of the miR-34 family, increased significantly in flurothyl-treated rat hippocampus tissue. More surprisingly, this upregulation occurred concurrently with accumulating astrocyte apoptosis, indicating the involvement of miR-34b-5p in seizures caused astrocyte apoptosis. Results from the in vitro experiments further demonstrated that miR-34b-5p directly targeted Bcl-2 mRNA, translationally repressed Bcl-2 protein, and thus modulated cell apoptosis by influencing Bcl-2, Bax, and Caspase-3.Conclusion: Our findings prove microRNAs play a role in mediating recurrent convulsions-induced astrocyte death and further indicate that miR-34b-5p could acts as a regulator for astrocyte apoptosis induced by recurrent seizures. [ABSTRACT FROM AUTHOR]

Background: It is well known that epigenetic modifications play an important role in controlling the regulation of gene expression during the development. Our previous studies have demonstrated that the expression of fetal troponin I gene (also called slow skeletal troponin I, ssTnI) is predominated in the fetal stage, reduced after birth and disappeared in the adulthood. The mechanism underlying the developmentally related ssTnI gene regulation is not clear. In this study, we have explored the epigenetic role of DNA methylation in the regulation of ssTnI expression in the heart during the development. Results: The DNA methylation levels of CpG island and CpG dinucleotides region were detected using methylation specific PCR (MSP) and bisulfite sequence PCR (BSP) in 2000 bp upstream and 100 bp upstream of ssTnI gene promoter. Real time RT-PCR and Western blot were used to detect ssTnI mRNA and protein expression levels. We found that DNA methylation levels of the CpG dinucleotides region in ssTnI gene promoter were increased with the development, corresponding to a decreased expression of ssTnI gene in mouse heart. However the DNA methylation levels of CpG islands in this gene were not changed during the development. Application of a methylation inhibitor, 5-Azacytidine, in cultured myocardial cells partially prevented the decline of ssTnI expression. Conclusion: Our results indicate that DNA methylation, as an epigenetic intervention, plays a role in the regulation of the fetal TnI gene expression in the heat during the development. [ABSTRACT FROM AUTHOR]

Highly detached TiO2 nanotube arrays (TiO2-NTAs) were fabricated by anodization method using electrolyte with high water content. CdS and CdSe quantum dots (QDs) were co-deposited on the TiO2-NTAs. The results showed that the CdS and CdSe QDs were uniformly deposited on both the outer wall and inner tube of TiO2-NTAs. The photocatalytic performance of the as-prepared (CdS-CdSe)/TiO2-NTAs was tested by degradation of methyl orange with 0.2 M Na2S and Na2SO3 as sacrificial reagents under visible light (λ>400 nm). It was found that the photodegradation rate reached as high as 95.1% in 2 h. Also, a reasonable degradation rate of 87.5% was achieved after 3 cycles, suggesting a good stability of the as-prepared (CdS-CdSe)/TiO2-NTAs. [ABSTRACT FROM AUTHOR]

Prenatal alcohol exposure leads to congenital heart abnormal development, its mechanisms are still unknown. Recent reports have associated alcohol exposure with histone H3 acetylation. In the present study, we have performed the experiments to test the hypothesis that histone H3K14 acetylation is the key role in the fetal heart leads to over-expression of cardiac specific genes DHAND and EHAND caused by prenatal alcohol exposure. Seventy pregnant C57BL/6 mice were divided randomly into seven groups (n=10). They were the untreated group, dimethyl sulfoxide group, alcohol exposure group, curcumin treatment group, both alcohol and curcumin treatment group, SAHA treatment group, both alcohol and SAHA treatment group. Fetal mouse hearts were collected on embryonic day 14.5. The changes of HATs activities, the acetylation levels of histone H3K14 (H3K14ac), the expression levels of cardiac specific genes DHAND and EHAND, and structure of chromatin were determined. Our data indicates that curcumin and SAHA significantly reduces and increases the activities of HATs and the levels of histone H3K14ac in fetal hearts, respectively. The expression of DHAND and EHAND is significantly down-regulated and up-regulated in the groups treated with curcumin and SAHA. Furthermore, our results from ChIP assays have shown that the histone H3K14ac connects with the DHAND and EHAND genes are significantly inhibited by curcumin and simulated by SAHA. Our study suggests that prenatal alcohol exposure causes the over-expression of DHAND and EHAND by increasing H3K14ac in mice. [ABSTRACT FROM AUTHOR]

BMP2 signaling pathway plays critical roles during heart development, Smad4 encodes the only common Smad protein in mammals, which is a pivotal nuclear mediator. Our previous studies showed that BMP2 enhanced the expression of cardiac transcription factors in part by increasing histone H3 acetylation. In the present study, we tested the hypothesis that Smad4 mediated BMP2 signaling pathway is essential for the expression of cardiac core transcription factors by affecting the histone H3 acetylation. We successfully constructed a lentivirus-mediated short hairpin RNA interference vector targeting Smad4 (Lv-Smad4) in rat H9c2 embryonic cardiac myocytes (H9c2 cells) and demonstrated that it suppressed the expression of the Smad4 gene. Cultured H9c2 cells were transfected with recombinant adenoviruses expressing human BMP2 (AdBMP2) with or without Lv-Smad4. Quantitative real-time RT-PCR analysis showed that knocking down of Smad4 substantially inhibited both AdBMP2-induced and basal expression levels of cardiac transcription factors GATA4 and Nkx2.5, but not MEF2c and Tbx5. Similarly, chromatin immunoprecipitation (ChIP) analysis showed that knocking down of Smad4 inhibited both AdBMP2-induced and basal histone H3 acetylation levels in the promoter regions of GATA4 and Nkx2.5, but not of Tbx5 and MEF2c. In addition, Lv-Smad4 selectively suppressed AdBMP2-induced expression of HAT p300, but not of HAT GCN5 in H9c2 cells. The data indicated that inhibition of Smad4 diminished both AdBMP2 induced and basal histone acetylation levels in the promoter regions of GATA4 and Nkx2.5, suggesting that Smad4 mediated BMP2 signaling pathway was essential for the regulation of GATA4 and Nkx2.5 by affecting the histone H3 acetylation in H9c2 cells. [ABSTRACT FROM AUTHOR]