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人脱嘌呤嘧啶核酸内切酶1(HAP1/Ref-1)蛋白的表达及亚细胞定位:其在人类疾病中作用的基础

Expression and subcellular localization of human AP endonuclease 1 (HAP1/Ref-1) protein: a basis for its role in human disease.

作者信息

Kakolyris S, Kaklamanis L, Giatromanolaki A, Koukourakis M, Hickson I D, Barzilay G, Turley H, Leek R D, Kanavaros P, Georgoulias V, Gatter K C, Harris A L

机构信息

Department of Cellular Science, John Radcliffe Hospital, University of Oxford.

出版信息

Histopathology. 1998 Dec;33(6):561-9. doi: 10.1046/j.1365-2559.1998.00541.x.

DOI:10.1046/j.1365-2559.1998.00541.x
PMID:9870152
Abstract

AIMS

Human AP endonuclease 1 (HAP1) plays a major role in the repair of apurinic/apyrimidinic (AP) sites in cellular DNA by catalysing hydrolytic cleavage of the phosphodiester backbone 5' to the site. HAP1 is also known to be a potent reduction-oxidation (redox) factor, regulating the binding activity of a number of transcription factors. The purpose of the present study was to examine the expression of HAP-1 in a wide range of human tissues.

METHODS AND RESULTS

Using a recently developed specific rabbit polyclonal antibody, we performed immunohistochemistry on paraffin-embedded tissue material. Nuclear staining was detected in crypt cells of the small and large intestine, epithelial cells of breast ducts, basal cells of the skin, alveolar cells of the lung, lymphocytes of the marginal zone of the spleen, in the surface epithelium and stromal cells of the ovary and the transitional epithelium of the bladder. Unexpectedly for a presumed nuclear protein, the staining pattern in some cell populations was mainly cytoplasmic (e.g. superficial cells of gastrointestinal tract, Langerhans cells, Leydig cells and spermatocytes, epithelium of the prostate glands), or both cytoplasmic and nuclear (e.g. epithelial cells of thymus, follicular thyroid cells, parietal cells of the stomach, glandular epithelial cells of the cervix, epithelial cells of exocrine pancreas).

CONCLUSION

This differential expression in a wide spectrum of cells is indicative of a potential multifunctional action of HAP1, not necessarily restricted to a role in the nucleus.

摘要

目的

人类脱嘌呤/脱嘧啶核酸内切酶1(HAP1)通过催化细胞DNA中脱嘌呤/脱嘧啶(AP)位点5'端磷酸二酯主链的水解切割,在修复AP位点中起主要作用。HAP1也被认为是一种强大的氧化还原因子,可调节多种转录因子的结合活性。本研究的目的是检测HAP1在多种人体组织中的表达。

方法与结果

我们使用最近开发的特异性兔多克隆抗体,对石蜡包埋的组织材料进行免疫组织化学检测。在小肠和大肠的隐窝细胞、乳腺导管上皮细胞、皮肤基底细胞、肺肺泡细胞、脾边缘区淋巴细胞、卵巢表面上皮和基质细胞以及膀胱移行上皮中检测到核染色。对于一种假定的核蛋白而言出乎意料的是,在一些细胞群体中的染色模式主要为细胞质(如胃肠道表层细胞、朗格汉斯细胞、睾丸间质细胞和精母细胞、前列腺上皮),或同时为细胞质和细胞核(如胸腺上皮细胞、甲状腺滤泡细胞、胃壁细胞、宫颈腺上皮细胞、外分泌胰腺上皮细胞)。

结论

在广泛细胞中的这种差异表达表明HAP1具有潜在的多功能作用,不一定局限于在细胞核中的作用。

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