Age-related impairment of the transcriptional responses to oxidative stress in the mouse heart
Age-related impairment of the transcriptional responses to oxidative stress in the mouse heart
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DOI：
10.1152/physiolgenomics.00172.2002
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发表时间：
2003-04-16
影响因子：
4.6
通讯作者：
Prolla, TA
中科院分区：
文献类型：
--
作者：
Edwards, MG;Sarkar, D;Prolla, TA
为了研究心脏对氧化应激的转录反应及其如何随年龄变化，我们检测了单次腹腔注射百草枯（50 mg/ kg）处理的年轻（5月龄）、中年（15月龄）和老年（25月龄）C57 BL/6小鼠的心脏基因表达谱。小鼠在百草枯处理后0、1、3、5和7 h处死，用高密度寡核苷酸微阵列获得基因表达谱。在微阵列上代表的9，977个基因中，年轻小鼠中的249个转录本、中年小鼠中的298个转录本和老年小鼠中的256个转录本的mRNA水平显示出显着变化（方差分析，P < 0.01）。其中，共有55份转录本被确定为对所有年龄组的百草枯有反应。在所有年龄组中通常诱导的基因包括与压力、炎症、免疫和生长因子反应相关的基因。有趣的是，只有年轻的小鼠表现出GADD 45的所有三种亚型的表达显着增加，GADD 45是一种DNA损伤反应基因。此外，百草枯诱导的立即早期反应基因数量在较年轻的动物中要高得多。这些结果表明，在转录水平上，有一个特定的诱导途径在小鼠心脏的氧化应激反应与年龄相关的损害。
To investigate the transcriptional response to oxidative stress in the heart and how it changes with age, we examined the cardiac gene expression profiles of young (5-mo-old), middle-aged (15-mo-old), and old (25-mo-old) C57BL/6 mice treated with a single intraperitoneal injection of paraquat ( 50 mg/ kg). Mice were killed at 0, 1, 3, 5, and 7 h after paraquat treatment, and the gene expression profile was obtained with high-density oligonucleotide microarrays. Of 9,977 genes represented on the microarray, 249 transcripts in the young mice, 298 transcripts in the middle-aged mice, and 256 transcripts in the old mice displayed a significant change in mRNA levels (ANOVA, P < 0.01). Among these, a total of 55 transcripts were determined to be paraquat responsive for all age groups. Genes commonly induced in all age groups include those associated with stress, inflammatory, immune, and growth factor responses. Interestingly, only young mice displayed a significant increase in expression of all three isoforms of GADD45, a DNA damage-responsive gene. Additionally, the number of immediate early response genes (IEGs) found to be induced by paraquat was considerably higher in the younger animals. These results demonstrate that, at the transcriptional level, there is an age-related impairment of specific inducible pathways in the response to oxidative stress in the mouse heart.