Caveolin induces cardioprotection through epigenetic regulation.
Bottom Line: Cav-1 KO mouse also decreased the translocation of forkhead transcription factor (FOXO3a) to the nucleus and reduced the induction of the expression of SIRT-1 in the preconditioned heart.Cardioprotective property of Cav-1 was further confirmed by reduced ventricular function, increased cardiomyocyte apoptosis, increased expression of junas kinase (JNK) and Bax and decreased expression of phospho-adenosine monophosphate-activated protein kinase (AMPK), phospho-AKT and B cell lymphoma-2 (Bcl-2) in Cav-1 KO preconditioned heart.The results clearly indicate that Cav-1 induces cardioprotection through epigenetic regulation.
Affiliation: Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, CT 06-030-1110, USA.Show MeSH
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Mentions: We then studied the histone modification histone acetylation and methylation were studied, which are the best characterized modification for epigenetics regulation. In this investigation, mainly we studied the methylation and acetylation of H3 and H4 histone after acid extraction of histone proteins. WT PC heart showed high level of expression of acetylated H3 and H4 histone proteins compared to the Cav-1 PC as well as Cav-1 I/R and WT I/R groups. For methylation of histone, two targets were selected (i) histone H3 lysine 9 (H3K9) and (ii) histone H3 lysine 27 (H3K27). Both H3K9 and H3K27 showed high level of expression in WT I/R and Cav-1 I/R group and also in Cav-1 PC group whereas WT PC group showed negligible level of expression. G9a, also known as Euchromatic histone lysine N-methyltransferase 2 (EHMT2), is a member of the family histone lysine methyltransferase. G9a protein also showed high level of expression in both WT I/R and Cav-1 I/R group and also in Cav-1 PC group where as WT PC group showed negligible level of expression (Fig. 3).
Affiliation: Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, CT 06-030-1110, USA.