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仓鼠过氧化物酶体增殖物激活受体haPPARγ的cDNA克隆及其转录活性的表征

cDNA cloning and characterization of the transcriptional activities of the hamster peroxisome proliferator-activated receptor haPPAR gamma.

作者信息

Aperlo C, Pognonec P, Saladin R, Auwerx J, Boulukos K E

机构信息

Centre de Biochimie, Faculte des Sciences, Nice, France.

出版信息

Gene. 1995 Sep 11;162(2):297-302. doi: 10.1016/0378-1119(95)00196-d.

Abstract

We have isolated a cDNA corresponding to the hamster peroxisome proliferator-activated receptor haPPAR gamma, a member of the steroid nuclear hormone receptor superfamily of transcription factors. haPPAR gamma mRNA is highly expressed in adipose tissue, and is expressed in lung, heart, kidney, liver and spleen to a lower extent. Thus, haPPAR gamma may function in activating the transcription of target genes in a variety of tissues, including those not particularly subjected to peroxisomal beta-oxidation. haPPAR gamma binds efficiently in the presence of retinoid X receptor alpha (RXR alpha) to a peroxisome proliferator response element (PPRE) first identified in the acyl-CoA oxidase (ACO) promoter, the rate-limiting enzyme of peroxisomal beta-oxidation. The gene (ACO) encoding this enzyme has been previously shown to be under the transcriptional control of mouse PPAR (mPPAR). Although binding of haPPAR gamma/RXR alpha on the PPRE of the ACO promoter in vitro is similar to that observed for mPPAR/RXR alpha, we show that the transcriptional activities of mPPAR and haPPAR gamma are regulated differently in vivo in response to peroxisome proliferators and heterodimerization with RXR.

摘要

我们分离出了一种与仓鼠过氧化物酶体增殖物激活受体haPPARγ相对应的cDNA,它是转录因子类固醇核激素受体超家族的成员。haPPARγ mRNA在脂肪组织中高度表达,在肺、心脏、肾脏、肝脏和脾脏中的表达程度较低。因此,haPPARγ可能在多种组织中激活靶基因的转录,包括那些并非特别受限于过氧化物酶体β氧化的组织。在视黄酸X受体α(RXRα)存在的情况下,haPPARγ能有效地与首先在酰基辅酶A氧化酶(ACO)启动子中鉴定出的过氧化物酶体增殖物反应元件(PPRE)结合,ACO是过氧化物酶体β氧化的限速酶。先前已表明,编码该酶的基因(ACO)受小鼠PPAR(mPPAR)的转录调控。尽管在体外,haPPARγ/RXRα在ACO启动子的PPRE上的结合与mPPAR/RXRα的情况相似,但我们发现,在体内,mPPAR和haPPARγ的转录活性在响应过氧化物酶体增殖剂以及与RXR异源二聚化时受到不同的调控。

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