Early onset of age related hearing loss in LDHB knock out mouse

Chan Bae Park
일반대학원 의생명과학과
The Graduate School, Ajou University
Publication Year
LDHBHearing loss
Alternative Abstract
Age related hearing loss (AHL) is a main feature of mammalian aging and is the most common sensory dysfunction in the elderly. AHL is associated with an age depended loss of sensory hair cell, spiral ganglion neurons, and stria vascularis cell in the inner ear(Gates and Mills,2005 and Yamasoba et al., 2007). The progressive loss of these cells finally results in hearing loss because hair cells and cochlear neuron cells do not regenerate. Mitochondria are key of energy supply, cellular redox balance, signaling and regulation of intrinsic apoptosis in inner ear, especially in the high energy demanding cells, such as hair cells and neuron cells (Hengchao, Chen et al., 2014). Lactate dehydrogenates B is important enzyme in maintaining high level of pyruvate which in the presence of oxygen will be further metabolized in the TCA cycle to produce NADH and FADH2 for oxidative phosphorylation in the mitochondria. This study aimed to observe the metabolism study of Age-related hearing loss in LDHB knockout mice. In response to deletion of LDHB gene in mouse caused early onset of age related hearing loss, as increase of high frequency threshold, hair cell death, which are the typical features of Age-related hearing loss. We investigate the molecular mechanism of hearing loss caused by LDHB deficiency by using in vitro hair cell UB-OC1. We found that differentiated UB-OC1 showed LDHB and increase of the mitochondrial function: mitochondrial respiratory subunits and MMP enhanced, increase of ATP and NAD+/NADH ratio were accompanied. LDHB knock down decreased mitochondrial function in differentiated UB-OC1 cell, the decrease of NAD+ and increase of HIF1a which probably cause mitochondrial dysfunction. LDHB knock down sensitized hair cell to antibiotics which support important clinical information.

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Graduate School of Ajou University > Department of Biomedical Sciences > 3. Theses(Master)
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