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
- 1 Department of Animal Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea
Received: July 10, 2015 Accepted: August 23, 2015 Published: August 29, 2015https://doi.org/10.18632/aging.100800
How to Cite
CMP-Neu5Ac hydroxylase (Cmah) disruption caused several abnormalities and diseases including hearing loss in old age. However, underling molecular mechanisms that give rise to age-related hearing loss (AHL) in Cmah-null mouse are still obscure. In this study, Cmah-null mice showed age-related decline of hearing associated with loss of sensory hair cells, spiral ganglion neurons, and/or stria vascularis degeneration in the cochlea. To identify differential gene expression profiles and pathway associated with AHL, we performed microarray analysis using Illumina MouseRef-8 v2 Expression BeadChip and pathway-focused PCR array in the cochlear tissues of Cmah-null mouse. Pathway and molecular mechanism analysis using differentially expressed genes provided evidences that altered biological pathway due to oxidative damage by low expressed antioxidants and dysregulated reactive oxygen species (ROS) metabolism. Especially, low sirtuin 3 (Sirt3) gene expressions in Cmah-null mice decreased both of downstream regulator (Foxo1 and MnSod) and regulatory transcription factor (Hif1α and Foxo3a) gene expression. Taken together, we suggest that down-regulation of Sirt3 expression leads to oxidative stress and mitochondrial dysfunction by regulation of ROS and that it could alter various signaling pathways in Cmah-null mice with AHL
AHL: age-related hearing loss; Sirt3: sirtuin3; Cmah: CMP-N-acetylneuraminic acid hydroxylase; ROS: reactive oxygen species; KEGG: Kyoto Encyclopedia of Genes and Genome; DAVID: Database for Annotation, Visualization and Integrated Discovery; WT: wild-type; Hif1α: hypoxia-inducible factor 1-alpha; Foxo3a: forkhead box O3a; Foxo1: folkhead box protein O; MnSod: mamganese superoxide dismutase 2; RT-qPCR: quantitative real-time polymerase chain reaction; SV: scala vestibule; SM: scala media; ST: scala tympani; SG: spiral ganglion; BM: basilar membrane; RM: reissner's membrane; Sv: stria vascularis; OT: otoconia; OM: otolithic membrane; NHC & SC: neuroepithelial hair cells and supporting cells; HC: hair cells; OHCs: outer hair cells; SL: spiral lamina..