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Analysis of the stress response in oral lesions by using Nrf2 gene knockout mouse

Nrf2基因敲除小鼠口腔病变应激反应分析

基本信息

批准号：
12671924
负责人：
YANAGAWA Toru
金额：
$ 2.11万
依托单位：
Univ. of Tsukuba
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671924/
关键词：
Nrf2 IRON ION FERRITIN OXIDATIVE STRESS BHA

项目摘要

The purpose of this study is to analyze how the transcription factor Nrf2 is associated with oral diseases. As fundamental study, we investigated the role of Nrf2 against oxidative stress and confirmed that the oxidative stress proteins, such as hemeoxygenase, peroxireoxin MSP23, A170, are under control of Nrf2 regulation. We also found MSP23 was induced by BHA treatment. Through these experiments we found the phenotype of Nrf2 mice was the decolorization of the maxillary incisor. We analyzed this phenomenon to know the significance of Nrf2 in oral desease. At first the incisor samples were fixed in ethanol and dehydraded by critical point drying method, and we observed the suface of the incisors with scanning electron microscope. There was no difference among the homo, hetero and wild type mice. We quantified the Ca, P, and Fe ion content with energy disparative micro X ray analysis and found there were significant difference among the mice. Iron ion content decreased significantly in knockout mice, though Ca and P content was not different. We estimated the association the iron ion and oral disease caused by nrf2 gene disruption. To know how the iron acted on the incisor decolorization, we investigated the ferritin and iron ion localization by using in situ hybridization, immunohistochemistry and iron staining. We found there were abnormal iron deposition and the ameloblast was damaged. Our results suggested Nrf2 affected on the oral diseases through abnormal iron deposition.

本研究的目的是分析转录因子Nrf2与口腔疾病的关系。作为基础研究，我们研究了Nrf2在抗氧化应激中的作用，证实了氧化应激蛋白如血红素加氧酶、过氧化物酶MSP23、A170等均受Nrf2调控。我们还发现BHA处理诱导了MSP23。通过这些实验，我们发现Nrf2小鼠的表型是上颌门牙的脱色。通过对这一现象的分析，了解Nrf2在口腔疾病中的意义。首先将切牙样品固定在乙醇中，用临界点干燥法脱水，用扫描电镜观察切牙表面。在同种、异种和野生型小鼠之间没有差异。我们用能量差微X射线分析定量了Ca、P和Fe离子的含量，发现小鼠之间存在显著差异。敲除小鼠体内铁离子含量显著降低，钙、磷含量无显著差异。我们估计了铁离子与nrf2基因破坏引起的口腔疾病的关系。为了了解铁对切牙脱色的作用机制，我们采用原位杂交、免疫组织化学和铁染色等方法研究了铁蛋白和铁离子的定位。发现铁沉积异常，成釉细胞受损。我们的结果提示Nrf2通过异常铁沉积作用于口腔疾病。