PDF(Pubmed)
Abstract：
We published the first paper to characterize GPX2 (aka GSHPx-GI) as a selenoenzyme with glutathione peroxidase activity in 1993. Among the four Se-GPX isozymes, GPX1-4, GPX1 and GPX2 are closely related in terms of structure, substrate specificities, and subcellular localization. What sets them apart are distinct patterns of gene regulation, tissue distribution and response to selenium. While we identified the digestive tract epithelium as the main site of GPX2 expression, later work has shown GPX2 is found more widely in epithelial tissues with concentration of expression in stem cell and proliferative compartments. GPX2 expression is regulated over a wide range of levels by many pathways, including NRF2, WNT, p53, RARE and this often results in attaching undue significance to GPX2 as GPX2 is only a part of a system of hydroperoxidase activities, including GPX1, peroxiredoxins and catalase. These other activities may play equal or greater roles, particularly in cell lines cultured without selenium supplementation and often with very low GPX2 levels. This could be assessed by examining levels of mRNA and protein among these various peroxidases at the outset of studies. As an example, it was found that GPX1 responds to the absence of GPX2 in mouse ileum and colon epithelium with higher expression. As such, both Gpx1 and Gpx2 had to be knocked out in mice to produce ileocolitis. However, we note that the actual role of GPX1 and GPX2 in relation to peroxiredoxin function is unclear. There may be an interdependence that requires only low amounts of GPX1 and/or GPX2 in a supporting role to maintain proper peroxiredoxin function. GPX2 levels may be prognostic for cancer progression in colon, breast, prostate and liver, however, there is no consistent trend for higher or lower levels to be favorable.
摘要：
我们在1993年发表了第一篇论文，将GPX2（又名GSHPx-GI）表征为具有谷胱甘肽过氧化物酶活性的硒酶。在四种Se-GPX同工酶中，GPX1-4、GPX1和GPX2在结构上密切相关，底物特异性，和亚细胞定位。使它们与众不同的是不同的基因调控模式，组织分布和对硒的反应。虽然我们确定消化道上皮是GPX2表达的主要位点，后来的研究表明,GPX2在上皮组织中更广泛地发现,在干细胞和增殖区室中有较高的表达浓度.GPX2的表达在广泛的水平上受到许多途径的调节。包括NRF2,WNT,p53，RARE，这通常导致对GPX2的过分重视，因为GPX2只是氢过氧化物酶活性系统的一部分，包括GPX1、过氧化物酶和过氧化氢酶。这些其他活动可能发挥同等或更大的作用，特别是在不补充硒且通常GPX2水平非常低的细胞系中。这可以通过在研究开始时检查这些各种过氧化物酶中的mRNA和蛋白质水平来评估。作为一个例子,发现GPX1对小鼠回肠和结肠上皮中GPX2缺失有较高的表达响应。因此，Gpx1和Gpx2都必须在小鼠中敲除以产生回肠结肠炎。然而,我们注意到GPX1和GPX2对过氧化物酶功能的实际作用尚不清楚.可能存在仅需要少量GPX1和/或GPX2起支持作用以维持适当的过氧化物氧还蛋白功能的相互依赖性。GPX2水平可能是结肠癌进展的预后因素，乳房,前列腺和肝脏,然而,没有一致的趋势，更高或更低的水平是有利的。
