Hypoxic regulation of cytoglobin and neuroglobin expression in human normal and tumor tissues.
Hypoxic regulation of cytoglobin and neuroglobin expression in human normal and tumor tissues.
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DOI：
10.1186/1475-2867-10-33
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发表时间：
2010-09-09
影响因子：
5.8
通讯作者：
Allalunis-Turner J
中科院分区：
文献类型：
--
作者：
Emara M;Turner AR;Allalunis-Turner J
细胞红蛋白（Cygb）和神经红蛋白（Ngb）是最近发现的在脊椎动物组织中表达的珠蛋白分子。在体外和体内缺氧和/或缺血条件下，Cygb和Ngb的上调增加细胞存活，表明可能通过预防氧化损伤发挥保护作用。我们以前已经表明，Ngb在人多形性胶质母细胞瘤（GBM）细胞系中表达，并且其转录本和蛋白质的表达在暴露于生理相关水平的缺氧后可以显著增加。在这项研究中，我们扩展了这项工作，以确定Cygb是否也在GBM细胞中表达，以及其表达是否在缺氧条件下增强。我们还比较了Cygb和Ngb在人类原发性肿瘤标本（包括脑肿瘤）以及人类正常组织中的表达。碳酸酐酶IX（CA IX）的免疫反应性，缺氧诱导的金属酶，催化水合CO2碳酸氢盐，被用作缺氧的内源性标志物。Cygb转录本和蛋白质在人GBM细胞中表达，并且在低氧下孵育48 h后，这种表达在大多数细胞中显著增加。我们还发现Cygb和Ngb在正常组织和人类原发性癌症（包括GBM）中表达。在正常组织中，Cygb和Ngb表达仅限于不同的细胞类型，在导管细胞中尤其突出。此外，某些正常器官（例如胃底、小肠）显示Ngb、Cygb和CA IX的不同区域共定位。在大多数肿瘤中，Ngb免疫反应性显著大于Cygb。与先前的体外结果一致，CA IX阳性染色的肿瘤区域也对Ngb和Cygb阳性，表明Ngb和Cygb的缺氧上调也发生在体内。我们在GBM细胞系和人类肿瘤组织中发现Cygb/Ngb的缺氧上调，这表明这些珠蛋白分子可能是允许癌细胞在缺氧微环境中生存的防御机制的一部分。
Cytoglobin (Cygb) and neuroglobin (Ngb) are recently identified globin molecules that are expressed in vertebrate tissues. Upregulation of Cygb and Ngb under hypoxic and/or ischemic conditions in vitro and in vivo increases cell survival, suggesting possible protective roles through prevention of oxidative damage. We have previously shown that Ngb is expressed in human glioblastoma multiforme (GBM) cell lines, and that expression of its transcript and protein can be significantly increased after exposure to physiologically relevant levels of hypoxia. In this study, we extended this work to determine whether Cygb is also expressed in GBM cells, and whether its expression is enhanced under hypoxic conditions. We also compared Cygb and Ngb expression in human primary tumor specimens, including brain tumors, as well as in human normal tissues. Immunoreactivity of carbonic anhydrase IX (CA IX), a hypoxia-inducible metalloenzyme that catalyzes the hydration of CO2 to bicarbonate, was used as an endogenous marker of hypoxia. Cygb transcript and protein were expressed in human GBM cells, and this expression was significantly increased in most cells following 48 h incubation under hypoxia. We also showed that Cygb and Ngb are expressed in both normal tissues and human primary cancers, including GBM. Among normal tissues, Cygb and Ngb expression was restricted to distinct cell types and was especially prominent in ductal cells. Additionally, certain normal organs (e.g. stomach fundus, small bowel) showed distinct regional co-localization of Ngb, Cygb and CA IX. In most tumors, Ngb immunoreactivity was significantly greater than that of Cygb. In keeping with previous in vitro results, tumor regions that were positively stained for CA IX were also positive for Ngb and Cygb, suggesting that hypoxic upregulation of Ngb and Cygb also occurs in vivo. Our finding of hypoxic up-regulation of Cygb/Ngb in GBM cell lines and human tumor tissues suggests that these globin molecules may be part of the repertoire of defense mechanisms that allow cancer cells to survive in hypoxic microenvironments.
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影响因子：
9.8
作者：
Johnston AL;Lun X;Rahn JJ;Liacini A;Wang L;Hamilton MG;Parney IF;Hempstead BL;Robbins SM;Forsyth PA;Senger DL
通讯作者：
Senger DL
DOI：
10.1073/pnas.93.18.9493
发表时间：
1996-09-03
影响因子：
11.1
作者：
Hochachka, PW;Buck, LT;Land, SC
通讯作者：
Land, SC
影响因子：
4.6
作者：
Burmester, T;Haberkamp, M;Hankeln, T
通讯作者：
Hankeln, T
影响因子：
14.9
作者：
Barrett T;Troup DB;Wilhite SE;Ledoux P;Rudnev D;Evangelista C;Kim IF;Soboleva A;Tomashevsky M;Marshall KA;Phillippy KH;Sherman PM;Muertter RN;Edgar R
通讯作者：
Edgar R
影响因子：
3.5
作者：
Fordel, Elke;Thijs, Liesbet;Dewilde, Sylvia
通讯作者：
Dewilde, Sylvia