The expression of key oxidative stress-handling genes in different brain regions in Alzheimer's disease
The expression of key oxidative stress-handling genes in different brain regions in Alzheimer's disease
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DOI：
10.1385/jmn:11:2:151
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发表时间：
1998-10-01
影响因子：
3.1
通讯作者：
Markesbery, WR
中科院分区：
文献类型：
--
作者：
Aksenov, MY;Tucker, HM;Markesbery, WR
阿尔茨海默病(AD)被认为与氧化应激有关。本研究采用逆转录-聚合酶链式反应(RT-PCR)技术，研究了10例AD患者和10例正常对照组大鼠海马区、顶下小叶和小脑中氧化应激调控关键基因的表达。测定锰、铜、锌超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶、谷胱甘肽还原酶、β-肌动蛋白和亲环素的mRNAs含量。这项研究表明，阿尔茨海默病大脑中转录水平的普遍下降可以显著调节基因对氧化应激的反应。为了确定特定的氧化应激处理基因转录在阿尔茨海默病中是被诱导还是被抑制，我们量化了“氧化应激处理基因/β-肌动蛋白”的比率，并在所有研究的脑区与控制值进行了比较。AD大鼠各脑区的Mn-SOD mRNA/β-肌动蛋白mRNA比值无明显变化，但顶下小叶中铜、锌-SOD mRNA/β-肌动蛋白mRNA比值升高。过氧化处理(CAT、GSH-PX和GSSG-R)mRNAs在AD患者的海马区和顶下小叶升高，但在小脑中不表达，这可能反映了AD严重病理脑区过氧化增加的保护性基因反应。这项研究的结果表明，ROS介导的损伤的大小的区域特异性差异，而不是氧化应激处理基因转录的初级缺陷，可能是导致AD大脑不同区域神经变性强度不同的原因。
Alzheimer's disease (AD) has been hypothesized to be associated with oxidative stress. in this study, the expression of key oxidative stress-handling genes was studied in hippocampus, inferior parietal lobule, and cerebellum of 10 AD subjects and 10 control subjects using reverse transcriptase-polymerase chain reaction (RT-PCR). The content of Mn-, Cu,Zn-superoxide dismutases (Mn- and Cu,Zn-SOD), catalase (CAT), glutathione peroxidase (GSH-rx), and glutathione reductase (GSSG-R) mRNAs, and the "marker genes" (beta-actin and cyclophilin) mRNAs was determined. This study suggests that gene responses to oxidative stress can be significantly modulated by the general decrease of transcription in the AD brain. To determine if the particular oxidative stress handling gene transcription was induced or suppressed in AD, the "oxidative stress-handling gene/beta-actin" ratios were quantified and compared with control values in all brain regions studied. The Mn-SOD mRNA/beta-actin mRNA ratio was unchanged in all regions of the AD brain studied, but an increase of the Cu,Zn-SOD mRNA/beta-actin mRNA ratio was observed in the AD inferior parietal lobule. The levels of peroxidation handling (CAT, GSH-Px, and GSSG-R) mRNAs normalized to beta-actin mRNA level were elevated in hippocampus and inferior parietal lobule, but not in cerebellum of AD patients, which may reflect the protective gene response to the increased peroxidation in the brain regions showing severe AD pathology. The results of this study suggest that region-specific differences of the magnitude of ROS-mediated injury rather than primary deficits of oxidative stress handling gene transcription are likely to contribute to the variable intensity of neurodegeneration in different areas of AD brain.