Center for Hearing and Deafness, State University of New York at Buffalo, Buffalo, NY, USA.
Neurobiol Aging. 2012 Aug;33(8):1842.e1-14. doi: 10.1016/j.neurobiolaging.2011.12.027. Epub 2012 Feb 1.
The biological mechanisms that give rise to age-related hearing loss (ARHL) are still poorly understood. However, there is growing recognition that oxidative stress may be an important factor. To address this issue, we measured the changes in the expression of cochlear oxidative stress and antioxidant defense-related genes in young (2 months old), middle-aged (12 months old), and old (21-25 months old) Fischer 344/NHsd (F344/NHsd) rats and compared gene expression changes with ARHL. A quantitative real-time reverse transcription polymerase chain reaction array revealed a significant age-related downregulation of only 1 gene, stearoyl-coenzyme A desaturase 1, and upregulation of 12 genes: 24-dehydrocholesterol reductase; aminoadipate-semialdehyde synthase; cytoglobin; dual oxidase 2; glutathione peroxidase 3; glutathione peroxidase 6; glutathione S-transferase, kappa 1; glutathione reductase; nicotinamide adenine dinucleotide phosphate (NAD(P)H) dehydrogenase, quinone 1; solute carrier Family 38, Member 5; thioredoxin interacting protein; and vimentin. Statistical analyses revealed significant correlations between gene expression and auditory function in 8 genes. Our results identified specific subsets of oxidative stress genes that appear to play an important role in ARHL in the Fischer 344/NHsd rat.
导致与年龄相关的听力损失（ARHL）的生物学机制仍知之甚少。然而，人们越来越认识到氧化应激可能是一个重要因素。为了解决这个问题，我们测量了年轻（2 个月大）、中年（12 个月大）和老年（21-25 个月大）Fischer 344/NHsd（F344/NHsd）大鼠耳蜗氧化应激和抗氧化防御相关基因表达的变化，并将基因表达变化与 ARHL 进行了比较。实时定量逆转录聚合酶链反应（qRT-PCR）阵列显示，只有 1 个基因，即硬脂酰辅酶 A 去饱和酶 1，表现出显著的年龄相关性下调，而 12 个基因则表现出上调：24-去氢胆固醇还原酶；天冬氨酸半醛合酶；细胞色素 b；双氧化酶 2；谷胱甘肽过氧化物酶 3；谷胱甘肽过氧化物酶 6；谷胱甘肽 S-转移酶，κ1；谷胱甘肽还原酶；烟酰胺腺嘌呤二核苷酸磷酸（NAD(P)H）脱氢酶醌 1；溶质载体家族 38 成员 5；硫氧还蛋白相互作用蛋白；和波形蛋白。统计分析显示，8 个基因的基因表达与听觉功能之间存在显著相关性。我们的研究结果确定了特定的氧化应激基因亚群，这些基因似乎在 Fischer 344/NHsd 大鼠的 ARHL 中发挥重要作用。
