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Anti-oxidant gene expression imbalance, aging and Down syndrome.

机译:抗氧化基因表达失衡,衰老和唐氏综合症。

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The expression of copper zinc superoxide dismutase (SOD1), manganese superoxide dismutase (SOD2), glutathione peroxidase (GPx), and catalase (CAT) genes have been detected in human skin fibroblast cells for 2 year normal child (control), 50 year old normal male and female and a 1 year old Down Syndrome (DS) male and female with established trisomy karyotype using the RT-PCR technique. Differential expression of these genes is quantified individually against a beta-Actin gene that has been employed as an internal control. The immunoblotting of cell lysate proteins with polyclonal antibodies exhibit SOD1 (16 kD), SOD2 (40 kD), GPx (23 and 92 kD), CAT (64 kD), and Actin (43 kD) as translational products. The results demonstrate that the enhancement in the level of mRNAs encoding SOD1 in DS male and female, as well as aged male and female are 51, 21, 31 and 50% respectively compared to the normal child (control). In SOD2, DS male and female display higher (176%) and lower (26%) levels of expression whereasaged male and female exhibit enhanced levels of expression (66 and 119%) respectively compared to the control. This study demonstrates that DS affects the female less than the male whereas in the aging process, the female is more prone to oxidative damage than the male. These results not only indicate that the level of GPx mRNA is constant except in DS male, which shows a downward regulation but that even CAT mRNA is upward regulated in aged as well as in DS males and females. These disproportionate changes in anti-oxidant genes, which are incapable of coping with over expressed genes, may contribute towards the aging process, dementia and Down syndrome.
机译:50岁的2岁正常儿童(对照)的人皮肤成纤维细胞中已检测到铜锌超氧化物歧化酶(SOD1),锰超氧化物歧化酶(SOD2),谷胱甘肽过氧化物酶(GPx)和过氧化氢酶(CAT)基因的表达正常男性和女性,以及使用RT-PCR技术建立了三体染色体核型的1岁唐氏综合症(DS)男性和女性。对这些基因的差异表达分别针对已经用作内部对照的β-Actin基因进行定量。用多克隆抗体对细胞裂解物蛋白的免疫印迹显示,SOD1(16 kD),SOD2(40 kD),GPx(23和92 kD),CAT(64 kD)和肌动蛋白(43 kD)为翻译产物。结果表明,与正常儿童(对照)相比,DS男性和女性以及老年男性和女性中编码SOD1的mRNA的水平分别提高了51%,21%,31%和50%。在SOD2中,DS男性和女性的表达水平较高(176%)和较低(26%),而与对照相比,老年男性和女性的表达水平则分别提高(66和119%)。这项研究表明,DS对女性的影响小于男性,而在衰老过程中,女性比男性更容易受到氧化损伤。这些结果不仅表明GPx mRNA的水平是恒定的,除了在DS雄性中表现出向下的调节,而且在雄性和DS雄性和雌性中甚至CAT mRNA也被上调。这些抗氧化基因的不成比例的变化无法应对过度表达的基因,可能会导致衰老,痴呆和唐氏综合症。

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