Tadros Sherif F, D'Souza Mary, Zhu Xiaoxia, Frisina Robert D
Department of Physiology, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia.
Apoptosis. 2008 Nov;13(11):1303-21. doi: 10.1007/s10495-008-0266-x.
To understand possible causative roles of apoptosis gene regulation in age-related hearing loss (presbycusis), apoptotic gene expression patterns in the CBA mouse cochlea of four different age and hearing loss groups were compared, using GeneChip and real-time (qPCR) microarrays. GeneChip transcriptional expression patterns of 318 apoptosis-related genes were analyzed. Thirty eight probes (35 genes) showed significant differences in expression. The significant gene families include Caspases, B-cell leukemia/lymphoma2 family, P53, Calpains, Mitogen activated protein kinase family, Jun oncogene, Nuclear factor of kappa light chain gene enhancer in B-cells inhibitor-related and tumor necrosis factor-related genes. The GeneChip results of 31 genes were validated using the new TaqMan Low Density Array (TLDA). Eight genes showed highly correlated results with the GeneChip data. These genes are: activating transcription factor3, B-cell leukemia/lymphoma2, Bcl2-like1, caspase4 apoptosis-related cysteine protease 4, Calpain2, dual specificity phosphatase9, tumor necrosis factor receptor superfamily member12a, and Tumor necrosis factor superfamily member13b, suggesting they may play critical roles in inner ear aging.
为了解凋亡基因调控在年龄相关性听力损失（老年性聋）中的可能致病作用，使用基因芯片和实时（qPCR）微阵列比较了四个不同年龄和听力损失组的CBA小鼠耳蜗中的凋亡基因表达模式。分析了318个凋亡相关基因的基因芯片转录表达模式。38个探针（35个基因）显示出表达上的显著差异。显著的基因家族包括半胱天冬酶、B细胞白血病/淋巴瘤2家族、P53、钙蛋白酶、丝裂原活化蛋白激酶家族、Jun癌基因、B细胞中κ轻链基因增强子的核因子抑制剂相关基因和肿瘤坏死因子相关基因。使用新型TaqMan低密度阵列（TLDA）对31个基因的基因芯片结果进行了验证。八个基因显示出与基因芯片数据高度相关的结果。这些基因是：激活转录因子3、B细胞白血病/淋巴瘤2、Bcl2样1、半胱天冬酶4凋亡相关半胱氨酸蛋白酶4、钙蛋白酶2、双特异性磷酸酶9、肿瘤坏死因子受体超家族成员12a和肿瘤坏死因子超家族成员13b，表明它们可能在内耳衰老中起关键作用。
