Increased mitochondrial DNA damage and decreased base excision repair in the auditory cortex of D-galactose-induced aging rats.

Abstract

Aging has been associated with mitochondrial DNA (mtDNA) common deletion (CD). Age changes in the central auditory system are well known to affect speech perception. Base excision repair (BER) is the major type of DNA repair in mitochondria. The current study was designed to investigate potential causative mechanisms of central presbycusis by using a rat mimetic aging model induced by subcutaneous administration of D-galactose (D-gal). Quantitative real-time PCR and Western blotting analyses were performed to identify the mtDNA 4834 bp deletion and selected mitochondrial DNA repair enzymes, DNA polymerase γ (pol γ) and 8-oxoguanine DNA glycosylase (OGG1). Cell apoptosis in the auditory cortex was detected using terminal deoxynucleotidyltransferase mediated UTP nick-end labeling (TUNEL). Our data showed that mtDNA 4834 bp deletion and TUNEL-positive cells were significantly increased and the expression of pol γ and OGG1 were remarkably down-regulated in the auditory cortex in D-gal-treated rats compared to control rats. During aging, increased mtDNA damage likely results from decreased DNA repair capacity in the auditory cortex. DNA repair enzymes such as pol γ and OGG1 may provide novel pharmacological targets to promote DNA repair and rescue the central auditory system in patients with degenerative diseases.

• Authors: Bei Chen, Yi Zhong, Wei Peng, Yu Sun, Yu-juan Hu, Yang Yang, Wei-jia Kong
• Journal: Molecular biology reports (Mol Biol Rep) Vol. 38 Issue 6 Pg. 3635-42 (Aug 2011) ISSN: 1573-4978 [Electronic] Netherlands
• PMID: 21104133 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Mitochondrial
• RNA, Messenger
• DNA Repair Enzymes
• Galactose

Topics

• Aging (drug effects, metabolism)
• Animals
• Apoptosis (drug effects)
• Auditory Cortex (drug effects, metabolism, pathology)
• Base Pairing (drug effects)
• Blotting, Western
• DNA Damage
• DNA Repair (drug effects)
• DNA Repair Enzymes (genetics, metabolism)
• DNA, Mitochondrial (drug effects, metabolism)
• Densitometry
• Galactose (administration & dosage, pharmacology)
• Gene Expression Regulation (drug effects)
• In Situ Nick-End Labeling
• Male
• RNA, Messenger (genetics, metabolism)
• Rats
• Rats, Sprague-Dawley
• Sequence Deletion (genetics)