Research Paper Volume 7, Issue 8 pp 579—594

Oxidative stress and ROS metabolism via down-regulation of sirtuin 3 expression in Cmah-null mice affect hearing loss


Figure 4. Molecular mechanisms of sirtuins, oxidative stress regulation, and Wnt signaling involved in Cmah-null mice. (A) IHC in cochlea of WT- and Cmah-null mouse for detection of Sirt3. Bar: 200 um. SV: scala vestibule, RM: reissner's membrane, SM: scala media, ST: scala tympani, Sv: stria vascularis, SL: spiral lamina. (B) Expression levels of sirtuins were determined by RT-qPCR of RNA samples from cochlear tissues of WT- and Cmah-null mice. (C) Expression of AHL related genes on the microarray data from cochlear tissues of Cmah-null mice. (D) Expression levels of genes involved in the regulatory factor of sirtuin, Wnt signaling, and mitochondrial functional regulation were determined by RT-qPCR of RNA samples from cochlear tissues of WT- and Cmah-null mice. (E) Measurement of mitochondrial activity in the cochlea of WT- and Cmah-null mice. Immunofluorescence was performed using a mitochondrial marker antibody. The intensity of the fluorescent signal indicates mitochondria numbers or the level of integrity. (F) Summary model describing the molecular mechanisms for sirtuins and oxidative stress regulation, Wnt signaling, and mitochondrial dysfunction by identified RT-qPCR results and array date set. The down-regulated Sirt3 lead to oxidative damage and mitochondrial dysfunction and could be alter various signaling pathways in Cmah-null mice with AHL. Sirt3-5: NAD-dependent protein deacetylase sirtuin3-5, Hif1α: Hypoxia-inducible factor 1-alpha, Foxo3a: Forkhead box O3, Foxo1: Forkhead box protein O1, MnSod: superoxide dismutase 2, mitochondrial, Lrp5-6: Low-density lipoprotein receptor-related protein 5-6, Wnt: Wingless, the Drosophila melanogaster segment-polarity gene, and Integrase-1 the vertebrate homologue, Gsk3β: Glycogen synthase kinase 3 beta, Cbr1: carbonyl reductase 1, Imp1: inner mitochondrial membrane peptidase-like, Mtfp1: mitochondrial fission process 1, RhoT2: Mitochondrial Rho GTPase 2, CytoC: Cytochrome C, Soc1-2: soluble oxidase component 1-2.