Characterization of the adrenal-specific antigen IZA (inner zone antigen) and its role in the steroidogenesis

Characterization of the adrenal-specific antigen IZA (inner zone antigen) and its role in the steroidogenesis
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DOI:
10.1016/j.mce.2003.11.025
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发表时间:
2004-02-27
影响因子:
4.1
通讯作者:
Okamoto, M
Okamoto, M
中科院分区:
医学2区
文献类型:
--
作者:
Min, L;Takemori, H;Okamoto, M

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内带抗原(IZA)是一种特异性表达于肾上腺皮质束状核和网状核的蛋白质。发现编码IZA的cDNA与编码先前报道的推定的膜相关孕酮受体(MPR)和TCDD诱导的25 kDa蛋白(25-Dx)的cDNA相同。从结构上看,MPR属于含有血红素结合结构域的蛋白质家族,孕酮被认为是该结构域的配体。实际上,当GST标记的IZA在大肠杆菌中表达并纯化时,纯化的GST-IZA具有棕色,在400 nm处具有最大吸光度。连二硫酸盐的加入使吸收峰移至420 nm,表明血红素结合功能。IZA在类固醇生成中的可能作用已经得到解决,并且已经报道了通过添加抗IZA单克隆抗体来抑制肾上腺类固醇生成。当COS-7细胞转化与适当的类固醇生成酶的IZA表达质粒的存在或不存在下,并测试其类固醇生成活性的质粒,21-羟基化的孕酮被发现特异性激活IZA过表达,这表明IZA参与孕酮代谢。总之,现有的证据表明,IZA可能在肾上腺束状核和网状核的功能中起重要作用。(C)2003爱思唯尔爱尔兰有限公司保留所有权利。
Inner zone antigen (IZA) is a protein specifically expressed in the zona fasciculata and reticularis of the adrenal cortex. The cDNA encoding IZA was found to be identical to that encoding the previously reported putative membrane-associated progesterone receptor (MPR) and the TCDD-induced 25 kDa protein (25-Dx). From its structure, MPR was classed as a member of a protein family containing a haeun-binding domain, and progesterone was proposed to be a ligand of this domain. Indeed, when GST-tagged IZA was expressed in Escherichia coli and purified, the purified GST-IZA had a brown colour with maximum absorbance at 400 nun. The addition of dithionate shifted the absorbance peak to 420 nm, suggesting a haem-binding function. The possible role of IZA in steroidogenesis has been addressed, and the inhibition of adrenal steroidogenesis by the addition of an anti-IZA monoclonal antibody has been reported. When COS-7 cells were transformed with plasmids for appropriate steroidogenic enzymes in the presence or absence of an IZA expression plasmid and tested for their steroidogenic activities, 21-hydroxylation of progesterone was found to be specifically activated by IZA overexpression, suggesting the involvement of IZA in progesterone metabolism. Taken together, the available evidence suggests that IZA may have an important role in the functions of the adrenal zona fasciculata and reticularis. (C) 2003 Elsevier Ireland Ltd. All rights reserved.