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The study on the morphogenesis of peroxisomes by the inhibition of the expression of transcription factors, PPARs.

通过抑制转录因子 PPAR 的表达来研究过氧化物酶体的形态发生。

基本信息

批准号：
10670011
负责人：
USUDA Nobuteru
金额：
$ 2.05万
依托单位：
Shinshu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670011/
关键词：
Peroxisomes transcripton factor morphogenesis cell organnelles

项目摘要

Peroxisomes appear in the cells, as cell organnelles of small size in cells and they increase the number and the size during embryonic development, by the administration of various chemicals called peroxisome proliferators, and by various external physiological stimuli. The object of the study is to elucidate the mechanism of these phenomena employing knock out mice as materials. The present study was attempted to show the mechanism regulating the morphogenesis of peroxisomes by transcription factors called PPARs, represented by PPARα. Two kinds of analyses were accomplished on PPARα knock out mouse and cultured cells inhibited the expression of PPARs by anti-sense RNA method. The results of former experiment have been present at the meetings and publications in journals, however, the latter experiments were to difficult to get results deserve publication.RESULTS: 1) Peroxisomes appear as small spherical cell organnelles in various embryonic organs, their size, number and enzymes increase along with development. 2) The proliferation of cells and peroxisomes occur in brown adipose tissues during cold acclimation, which are regulated by the activation of PPARs. 3) The activation of PPARα induce proliferation of hepatocytes and peroxisomes, fatty liver, and hepatocellular carcinoma. 4) PPARα regulates cell cycle.DISCUSSION: PPARα regulates the size of peroxisomes and the amount of peroxisomal enzymes, however, other factors may regulate their number. The morphogenesis of peroxisomes has been postulated that they appear as small particles, increase their size and the increase of the size result in the increase of the number. This hypothesis may not always true in every case of peroxisome proliferation. PPARα may also play important role in hepatocarcinogenesis by regulating cell cycle.

过氧化物酶体出现在细胞中，作为细胞中小尺寸的细胞器，并且它们在胚胎发育期间通过施用称为过氧化物酶体增殖剂的各种化学物质以及通过各种外部生理刺激来增加数量和尺寸。本研究的目的是以基因敲除小鼠为材料，阐明这些现象的机制。本研究试图阐明以过氧化物酶体激活受体α（PPARα）为代表的转录因子PPARs调控过氧化物酶体形态发生的机制。对PPARα基因敲除小鼠进行了两种分析，并采用反义RNA方法对培养细胞抑制PPARs表达进行了研究。结果：1）过氧化物酶体在胚胎各器官中均呈球形细胞器，其大小、数量和酶活性均随发育沿着而增加。2)在冷适应过程中，棕色脂肪组织中细胞和过氧化物酶体的增殖受到PPARs激活的调节。3)PPARα的活化可诱导肝细胞和过氧化物酶体的增殖、脂肪肝和肝细胞癌。4)PPARα调节细胞周期。讨论：PPARα调节过氧化物酶体的大小和过氧化物酶体酶的数量，然而，其他因素可能调节其数量。过氧化物酶体的形态发生被认为是以小颗粒的形式出现，并随着颗粒的增大而增大，颗粒的增大导致过氧化物酶体数量的增加。这一假设可能并不总是正确的过氧化物酶体增殖的每一个案件。PPARα可能通过调节细胞周期而在肝癌的发生发展中发挥重要作用。