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AGING PPAR AND HEPATIC PEROXISOMES

老化 PPAR 和肝过氧化物酶体

基本信息

批准号：
2012369
负责人：
MOSTAFA Zaki BADR
金额：
$ 9.96万
依托单位：
UNIVERSITY OF MISSOURI KANSAS CITY
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-08-15 至 2000-08-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2012369
关键词：
aging catalase coenzyme A enzyme activity laboratory rat liver function northern blottings peroxisome receptor receptor expression western blottings

项目摘要

DESCRIPTION (Adapted from applicant's abstract and specific aims): Several isoforms of the peroxisome proliferator-activated receptor (PPAR) have recently been discovered and implicated in the process of peroxisome proliferation. It is reported that while PPAR-alpha (PPAR-a) is responsible for the pleiotropic effects of peroxisome proliferators, PPAR-delta (PPAR-d) and PPAR-d may play a repressive role in this process. Tissues which are most responsive to peroxisome proliferators express high amount of PPAR-a and low amounts of the other two isoforms. Studies also show that fenofibrate, a peroxisome proliferator, enhanced the expression of hepatic PPAR-a. Preliminary data show a decline in basal and inducible levels of hepatic peroxisomal enzymes in aged animals. The investigators hypothesize that aged animals have lower levels of PPAR-a and/or higher levels of PPAR-a and PPAR-d, compared to young animals, and the expression of PPAR-a is not enhanced in livers of aged rats by peroxisome proliferators, to levels observed in young animals. The investigators will test this hypothesis by: (1) quantitating hepatic constitutive levels of the various PPAR isoforms in young (4,10 wk), mature (20 wk) and aged (50,100 wk). (2) determining the level of inducibility of PPAR-a in response to several structurally dissimilar peroxisome proliferators (WY-14,643, DEHP, clofibrate, PFOA) in these animals groups, (3) correlating levels of individual PPAR isoforms with peroxisomal enzyme activities in livers of various age group rats untreated and treated with peroxisome proliferators. The purpose of these experiments will be to investigate the relationship between levels of expression of the various PPAR isoforms and constitutive levels of peroxisomal enzyme activities as well as the extent of the pleiotropic response to peroxisome proliferators in the livers of young and aged animals. Recent published findings showing that inhibiting peroxisomal enzyme activities shortened the animal longevity and the fact that aged animals have reduced peroxisomal activities, necessitates an urgent evaluation of the possibly that the decline in these activities may contribute to the process of aging.

描述（根据申请人的摘要和具体目标改编）：几个过氧化物酶体增殖物激活受体（过氧化物酶体增殖物激活受体）的亚型最近被发现并与过氧化物酶体的过程有关增殖据报道，虽然PPAR-alpha（PPAR-a）是负责过氧化物酶体增殖物PPAR-d的多效性 PPAR-d可能在此过程中起抑制作用。组织是对过氧化物酶体增殖物最敏感的人表达大量的PPAR-a 和少量的其他两种异构体。研究还表明，过氧化物酶体增殖剂非诺贝特可增强肝细胞内 PPAR-a。初步数据显示，基础和诱导水平的下降，老年动物肝过氧化物酶体酶。调查人员假设老年动物的PPAR-a水平较低和/或PPAR-a水平较高，和PPAR-d，与年轻动物相比，PPAR-a的表达不是过氧化物酶体增殖剂增强老年大鼠肝脏中的过氧化物酶体增殖剂，在年轻的动物中观察到。研究者将通过以下方式检验这一假设： (1)定量各种过氧化物酶体增殖物受体亚型的肝脏组成性水平，幼龄（4、10周龄）、成熟（20周龄）和老龄（50、100周龄）。 (2)确定 PPAR-a的诱导水平响应于几种结构上不同的过氧化物酶体增殖物（WY-14，643、DEHP、氯贝特、PFOA），这些动物组，（3）将个体PPAR亚型的水平不同年龄组大鼠肝脏过氧化物酶体酶活性未处理和用过氧化物酶体增殖剂处理。施行本实验将调查水平之间的关系，不同的过氧化物酶体增殖物激活受体亚型的表达和组成性水平，过氧化物酶体酶活性以及多效性的程度青年和老年人肝脏对过氧化物酶体增殖物的反应动物最近发表的研究结果表明，抑制过氧化物酶体酶活性降低动物寿命，动物的过氧化物酶体活动减少，需要紧急治疗评估这些活动的减少可能有助于衰老的过程。