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

Abstract

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 (Hif1αand Foxo3α) 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.

• Authors: Deug-Nam Kwon, Woo-Jin Park, Yun-Jung Choi, Sangiliyandi Gurunathan, Jin-Hoi Kim
• Journal: Aging (Aging (Albany NY)) Vol. 7 Issue 8 Pg. 579-94 (Aug 2015) ISSN: 1945-4589 [Electronic] United States
• PMID: 26319214 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Reactive Oxygen Species
• Sirt3 protein, mouse
• Mixed Function Oxygenases
• CMPacetylneuraminate monooxygenase
• Sirtuin 3

Topics

• Animals
• Disease Models, Animal
• Ear, Inner (metabolism, pathology)
• Gene Expression Profiling
• Hearing Loss (genetics, metabolism, pathology)
• Mice, Inbred C57BL
• Mitochondria (metabolism)
• Mixed Function Oxygenases (genetics)
• Oxidative Stress
• Reactive Oxygen Species (metabolism)
• Sirtuin 3 (metabolism)
• Wnt Signaling Pathway