Caveolin induces cardioprotection through epigenetic regulation

Abstract

Lipid rafts represent a sub-compartment of the plasma membrane that co-ordinate and regulate varieties of signalling processes, whereas caveolins are the integral membrane protein of the lipid raft. Recent evidence demonstrated the pivotal role of caveolins in cardioprotection against ischaemic injury, although their mechanism of action is not clear. However, new understanding of epigenetic modification during ischaemia reperfusion suggests additional targeted approaches that have not been explored before. To study the role of caveolin on epigenetic regulation, isolated mouse heart was prepared from wild-type (WT) and caveolin-1 knockout (Cav-1 KO) mouse and preconditioned them with four cyclic episodes of ischaemia/reperfusion followed by 30 min. global ischaemia and 120 min. reperfusion. We found that Cav-1 KO mouse abolished the acetylation of histone (H3 and H4) and increased the methylation of histone in the preconditioned heart. The increased histone methylation was significantly correlated with an increased level of histone methyltranferase G9a protein and increased the level of histone decaetylase (HDAC) activity. 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.

Ischemic Preconditioning Confers Epigenetic Repression of Mtor and Induction of Autophagy Through G9a‐Dependent H3K9 Dimethylation

“…For example, there is evidence that the neuroprotective phenotype induced by IPC of the brain relies on epigenetic changes . Moreover, caveolin has been shown to induce cardioprotection through epigenetic alterations in preconditioned hearts and inhibition of histone deacetylase activity mitigates ischemic injury in isolated mouse hearts and reduces MI size in vivo . Although there is evidence for the role of histone acetylation in the cardioprotective effect of IPC, much less is known about histone methylation.…”

Farnesoid X receptor agonist decreases lipid accumulation by promoting hepatic fatty acid oxidation in db/db mice

“…Western blotting. The nuclear, cytosolic and membrane fractions were extracted from liver tissue as previously described (14). To obtain total proteins, liver tissues from the mice were lysed in a buffer containing 50 mM Tris-Hcl (pH 7.4), 150 mM NaCl, 1% Triton X-100, 0.1% SDS and 1 mM phenylmethylsulfonyl fluoride.…”

Resveratrol ameliorates cardiac oxidative stress in diabetes through deacetylation of NFkB-p65 and histone 3

“…Extraction of the nuclear protein fraction of heart tissue was performed using NE- histone proteins were extracted by the acid extraction method as described before [32]. Histone proteins (10ug) were resolved in 14% SDS gel and detected using Rabbit anti-H3 and Rabbit anti-Acetyl-H3K9 antibody (Cell signaling.…”