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无嘌呤/无嘧啶内切核酸酶(APE/ref-1)多功能DNA碱基切除修复基因在胎儿发育过程中以及成年大鼠脑和睾丸中的差异表达。

Differential expression of the apurinic / apyrimidinic endonuclease (APE/ref-1) multifunctional DNA base excision repair gene during fetal development and in adult rat brain and testis.

作者信息

Wilson T M, Rivkees S A, Deutsch W A, Kelley M R

机构信息

Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

出版信息

Mutat Res. 1996 Apr 2;362(3):237-48. doi: 10.1016/0921-8777(95)00053-4.

DOI:10.1016/0921-8777(95)00053-4
PMID:8637502
Abstract

The multifunctional mammalian apurinic/apyrimidinic (AP) endonuclease is responsible for the repair of AP sites in DNA. In addition, this enzyme has been shown to function as a redox factor facilitating the DNA binding capability of Jun-Jun homodimers and Fos-Jun heterodimers by altering their redox state and to be involved in calcium mediated transcriptional repression of the parathyroid hormone gene. Previous studies examining the tissue specific distribution of the AP endonuclease (APE) transcript and protein by Northern analysis and enzymatic assays, respectively, have shown that this gene is expressed in all tissues at relatively similar levels. In the current study, adult and fetal rat tissue sections were examined for the expression of the APE transcript in specific subpopulations of cells and during development by in situ hybridization. In the adult brain, the APE transcript showed a widespread, but heterogeneous pattern of expression. Predominant levels of transcript were detected in the suprachiasmatic nuclei, the supraoptic and paraventricular nuclei, the hippocampus and the cerebellum. During fetal development, transcript was detected in all somatic sites examined with very high levels in the thymus, liver and developing brain. Examination of the adult testis indicated that the expression of the transcript varies with the stage of spermatogenesis with the highest levels being present over round spermatids. These results provide evidence that the APE gene is not homogeneously expressed, but rather is found in subpopulations of cells in the brain and testes and during development.

摘要

多功能哺乳动物脱嘌呤/脱嘧啶(AP)内切核酸酶负责修复DNA中的AP位点。此外,已证明该酶作为一种氧化还原因子,通过改变Jun-Jun同二聚体和Fos-Jun异二聚体的氧化还原状态来促进其与DNA的结合能力,并且参与甲状旁腺激素基因的钙介导转录抑制。之前分别通过Northern分析和酶促测定来检测AP内切核酸酶(APE)转录本和蛋白质的组织特异性分布的研究表明,该基因在所有组织中的表达水平相对相似。在本研究中,通过原位杂交检测成年和胎鼠组织切片中特定细胞亚群以及发育过程中APE转录本的表达情况。在成年大脑中,APE转录本呈现出广泛但不均匀的表达模式。在视交叉上核、视上核和室旁核、海马体和小脑中检测到较高水平的转录本。在胎儿发育过程中,在所检查的所有体细胞部位均检测到转录本,在胸腺、肝脏和发育中的大脑中水平非常高。对成年睾丸的检查表明,转录本的表达随精子发生阶段而变化,在圆形精子细胞中水平最高。这些结果证明,APE基因并非均匀表达,而是在大脑和睾丸的细胞亚群以及发育过程中表达。

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