Figure 6
From: Histone deacetylase inhibitors mediate DNA damage repair in ameliorating hemorrhagic cystitis
Reactivation of Ogg1 in bladder muscle reduce pyroptosis mediate cell death.
(A) Immunoblot of cultured bladder muscle cells from wild type and Ogg1-knockout mice indicate the expression of affected proteins involved in pyroptotic cell death relative to ß-actin. (B) Mice were treated with CPX in the presence or absence of Mesna, nicotinamide (Nic), or SAHA. Representative bladder tissues from mice under the indicated treatments were subjected to rtPCR for Ogg1 mRNA expression. Mean quantitation of Ogg1 expression changes are represented below the blot relative to ß-actin expression. (C) Immunohistochemical localization of 5meC expression in the detrusor muscle was quantitated as a percentage of total cells per field. Data represent the mean ± S.D. **p value < 0.01; ***p value < 0.001, between groups by one way ANOVA (n = 3). (D) ROS induction by cyclophosphamide or acrolein in the bladder muscle can potentiate both NF-κB activation and 8-Oxo-dG accumulation. Mesna serves to sequester acrolein. The Ogg1 promoter DNA methylation (filled lollipops) by DNMTs is associated with de-acetylated histones and Ogg1 silencing to further 8-Oxo-dG accumulation. HDAC inhibitors and nicotinamide can reverse Ogg1 silencing by DNA de-methylation (open lollipops) and/or histone acetylation to inhibit 8-OxodG accumulation and pyroptotic cell death by way of NLRP3 and caspase1 activation for the expression of mature IL-1ß.
