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Effect of disturbing endocrine drug, DEHP, on microcyst formation in the epithelial cells.

干扰内分泌药物 DEHP 对上皮细胞微囊形成的影响。

基本信息

批准号：
11680571
负责人：
UEZATO Tadayoshi
金额：
$ 2.43万
依托单位：
Hamamatsu University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

Vacuolar H^+-ATPase(V-ATPase) is localized in organelles of the central vacuolar system such as lysosomes, coated vesicles, and the Golgi apparatus, and it plays an important role in maintaining the acidic enviroment in these compartments. We investigated the effects of di(2-ethylhexyl) phthalate (DEHP) on mouse liver lysosomes. After 2-3 weeks of oral administration in mice, a reduction in vacuolar H^+-ATPase, as determined by immunocytochemical analysis. When the mice were subsequently fed a normal diet for 1 week, V-ATPase, levels recovered to normal values. According to Northern blot analysis, V-ATPase subunit A mRNA decreased gradually with DEHP treatment. Enzyme cytochemical staining showed acid phosphatase to be present in lysosomes and late autophagosomes in normal animals as well as in DEHP-treated animals. But the number of late autophagosomes containing acid phosphatase increased clearly after DEHP treatment. These results suggest that, DEHP causes marked V-ATPase reduction in the liver lysosomal compartment and the effect to DEHP is reversible, and the effect of DEHP on protein expression is likely to be exerted at the transcriptional level. Thus in this study, we report that DEHP treatment causes a reduction in V-ATPase subunit A in the liver lysosomal compartment, which may accent for the inability to degrade excess cell organelles.

液泡H^+-ATP酶(V-ATPase)定位于中央液泡系统的细胞器，如溶酶体、包被囊泡和高尔基体，在维持这些区室的酸性环境中发挥着重要作用。我们研究了邻苯二甲酸二(2-乙基己基)酯 (DEHP) 对小鼠肝脏溶酶体的影响。小鼠口服给药2-3周后，通过免疫细胞化学分析测定，液泡H^+-ATP酶减少。随后给小鼠喂食正常饮食 1 周后，V-ATP 酶水平恢复至正常值。根据Northern印迹分析，V-ATP酶亚基A mRNA随着DEHP处理逐渐减少。酶细胞化学染色显示酸性磷酸酶存在于正常动物以及经 DEHP 处理的动物的溶酶体和晚期自噬体中。但DEHP处理后含有酸性磷酸酶的晚期自噬体数量明显增加。这些结果表明，DEHP导致肝脏溶酶体区室中V-ATP酶显着减少，并且对DEHP的影响是可逆的，并且DEHP对蛋白质表达的影响可能是在转录水平上发挥的。因此，在这项研究中，我们报告 DEHP 治疗会导致肝脏溶酶体区室中 V-ATP 酶亚基 A 的减少，这可能会加重无法降解多余细胞器的情况。