Expression pattern of oxidative stress and antioxidant defense-related genes in the aging Fischer 344/NHsd rat cochlea.

Expression pattern of oxidative stress and antioxidant defense-related genes in the aging Fischer 344/NHsd rat cochlea.
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DOI:
10.1016/j.neurobiolaging.2011.12.027
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发表时间:
2012-08
影响因子:
4.2
通讯作者:
Henderson D
Henderson D
中科院分区:
医学2区
文献类型:
--
作者:
Tanaka C;Coling DE;Manohar S;Chen GD;Hu BH;Salvi R;Henderson D

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导致年龄相关性听力损失(ARHL)的生物学机制仍不清楚。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进行比较。实时定量逆转录聚合酶链式反应显示,只有1个基因,硬脂酰辅酶A去饱和酶1与年龄相关显著下调,而12个基因上调:24-脱氢胆固醇还原酶;氨基己二酸-半醛合成酶;细胞球蛋白;双重氧化酶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kappa 1;谷胱甘肽还原酶;烟酰胺腺嘌呤二核苷酸磷酸脱氢酶;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。统计分析表明,有8个基因的表达与听功能显著相关。我们的结果确定了氧化应激基因的特定亚组,这些基因似乎在Fischer 344/nhsd大鼠的ARHL中发挥了重要作用。
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.
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