PMID- 23022596
OWN - NLM
STAT- MEDLINE
DCOM- 20130507
LR  - 20161125
IS  - 1878-5891 (Electronic)
IS  - 0378-5955 (Linking)
VI  - 294
IP  - 1-2
DP  - 2012 Dec
TI  - Age-related decline of the cytochrome c oxidase subunit expression in the 
      auditory cortex of the mimetic aging rat model associated with the common 
      deletion.
PG  - 40-8
LID - S0378-5955(12)00238-9 [pii]
LID - 10.1016/j.heares.2012.09.006 [doi]
AB  - The age-related deterioration in the central auditory system is well known to 
      impair the abilities of sound localization and speech perception. However, the 
      mechanisms involved in the age-related central auditory deficiency remain 
      unclear. Previous studies have demonstrated that mitochondrial DNA (mtDNA) 
      deletions accumulated with age in the auditory system. Also, a cytochrome c 
      oxidase (CcO) deficiency has been proposed to be a causal factor in the 
      age-related decline in mitochondrial respiratory activity. This study was 
      designed to explore the changes of CcO activity and to investigate the possible 
      relationship between the mtDNA common deletion (CD) and CcO activity as well as 
      the mRNA expression of CcO subunits in the auditory cortex of D-galactose 
      (D-gal)-induced mimetic aging rats at different ages. Moreover, we explored 
      whether peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha), 
      nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A 
      (TFAM) were involved in the changes of nuclear- and mitochondrial-encoded CcO 
      subunits in the auditory cortex during aging. Our data demonstrated that 
      d-gal-induced mimetic aging rats exhibited an accelerated accumulation of the CD 
      and a gradual decline in the CcO activity in the auditory cortex during the aging 
      process. The reduction in the CcO activity was correlated with the level of CD 
      load in the auditory cortex. The mRNA expression of CcO subunit III was reduced 
      significantly with age in the d-gal-induced mimetic aging rats. In contrast, the 
      decline in the mRNA expression of subunits I and IV was relatively minor. 
      Additionally, significant increases in the mRNA and protein levels of PGC-1alpha, 
      NRF-1 and TFAM were observed in the auditory cortex of D-gal-induced mimetic 
      aging rats with aging. These findings suggested that the accelerated accumulation 
      of the CD in the auditory cortex may induce a substantial decline in CcO subunit 
      III and lead to a significant decline in the CcO activity progressively with age 
      despite compensatory increases of PGC-1alpha, NRF-1 and TFAM. Therefore, CcO may be a 
      specific intramitochondrial site of age-related deterioration in the auditory 
      cortex, and CcO subunit III might be a target in the development of presbycusis.
CI  - Copyright (c) 2012 Elsevier B.V. All rights reserved.
FAU - Zhong, Yi
AU  - Zhong Y
AD  - Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, 
      China.
FAU - Hu, Yujuan
AU  - Hu Y
FAU - Peng, Wei
AU  - Peng W
FAU - Sun, Yu
AU  - Sun Y
FAU - Yang, Yang
AU  - Yang Y
FAU - Zhao, Xueyan
AU  - Zhao X
FAU - Huang, Xiang
AU  - Huang X
FAU - Zhang, Honglian
AU  - Zhang H
FAU - Kong, Weijia
AU  - Kong W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120927
PL  - Netherlands
TA  - Hear Res
JT  - Hearing research
JID - 7900445
RN  - 0 (DNA, Mitochondrial)
RN  - 0 (Nuclear Respiratory Factor 1)
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - 0 (Ppargc1a protein, rat)
RN  - 0 (Protein Subunits)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Tfam protein, rat)
RN  - 0 (Transcription Factors)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
SB  - IM
MH  - Aging/*genetics/*metabolism
MH  - Animals
MH  - Auditory Cortex/*metabolism/ultrastructure
MH  - Base Sequence
MH  - Cytochrome-c Oxidase Deficiency/enzymology/genetics
MH  - DNA, Mitochondrial/*genetics
MH  - Electron Transport Complex IV/chemistry/*genetics/*metabolism
MH  - Gene Expression
MH  - Male
MH  - Microscopy, Electron, Transmission
MH  - Nuclear Respiratory Factor 1/genetics/metabolism
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
MH  - Protein Subunits
MH  - RNA, Messenger/genetics/metabolism
MH  - RNA-Binding Proteins/genetics/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sequence Deletion
MH  - Transcription Factors/genetics/metabolism
EDAT- 2012/10/02 06:00
MHDA- 2013/05/08 06:00
CRDT- 2012/10/02 06:00
PHST- 2012/05/11 00:00 [received]
PHST- 2012/08/15 00:00 [revised]
PHST- 2012/09/20 00:00 [accepted]
PHST- 2012/10/02 06:00 [entrez]
PHST- 2012/10/02 06:00 [pubmed]
PHST- 2013/05/08 06:00 [medline]
AID - S0378-5955(12)00238-9 [pii]
AID - 10.1016/j.heares.2012.09.006 [doi]
PST - ppublish
SO  - Hear Res. 2012 Dec;294(1-2):40-8. doi: 10.1016/j.heares.2012.09.006. Epub 2012 
      Sep 27.