Relationship between AhR-related proteins and neurodegenerative diseases

AhR相关蛋白与神经退行性疾病的关系

• 批准号: 17590107
• 负责人: OHI Hiroshi
• 金额: $ 1.73万
• 依托单位: SHOWA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590107/
• 关键词: Ahr; ARNT; Xenopus laevis; neurodegenerative diseases; MPTP; 神経変性; シトクロムP450

By increasing the sample size of pole test, the exacerbation effect of 3MC on MPTP-induced symptom of Parkinson's disease was confirmed in mice. MPTP suppressed the increase of Cyp1a1 mRNA expression by 3MC administration in mouse brain. In contrast, the increase of Cyp1b1 mRNA by 3MC administration was not affected. Since AhR is participating in both expressional regulation of Cyp1a1 and Cyp1b1, it is intriguing that MPTP has had different effects on each isoform. In both the male and female adult Xenopus, xAhR protein was expressed in almost all organs examined. The expression of xArnt2 protein was observed only in brain while xArnt protein was expressed in liver, spleen, lung, heart, brain and testis. Through the early developmental stage, xAhR and xArnt proteins were expressed to various degrees. On the other hand, xArnt2 protein began to be expressed from stage 23 or later. Unlike in an unfertilized egg, xAhR mRNA was localized to the animal hemisphere in the fertilized egg. By 3MC treatment, the localization of xAhR mRNA to the animal hemisphere was not affected but translocation to the nucleus was observed in several cells., but it could recognize the movement to the nucleus of xAhR in plural cells. These results suggest that xAhR and xArnt have functions similar to those of mammalian homologues. In this study, Xenopus has been proved to be a good model for elucidate the relationship between AhR-related proteins and neurodegenerative diseases.

通过增加极点测试的样本量，在小鼠中证实了3MC对MPTP诱导的帕金森氏病症状的加重作用。 MPTP抑制了3MC在小鼠大脑中给予CYP1A1 mRNA表达的增加。相比之下，3MC给药的CYP1B1 mRNA增加不影响。由于AHR都参与CYP1A1和CYP1B1的表达调控，因此MPTP对每种同工型都有不同的影响，这很有趣。在雄性和雌性成年爪诺邦中，XAHR蛋白在几乎所有检查的器官中均表达。 XARNT2蛋白的表达仅在脑中观察到Xarnt蛋白在肝脏，脾，肺，心脏，脑，脑和睾丸中表达。在早期发育阶段，XAHR和XARNT蛋白均以各种程度表示。另一方面，XARNT2蛋白开始从第23阶段或更晚。与未施肥的卵不同，XAHR mRNA位于受精卵中的动物半球。通过3MC处理，在几个细胞中观察到XAHR mRNA在动物半球上的定位不受影响，但可以易于转移至细胞核。但是它可以识别出复数细胞中XAHR核的运动。这些结果表明XAHR和XARNN具有与哺乳动物同源物相似的功能。在这项研究中，已被证明是阐明与AHR相关蛋白与神经退行性疾病之间关系的良好模型。