High mobility group box (HMGB) proteins of Plasmodium falciparum:: DNA binding proteins with pro-inflammatory activity
High mobility group box (HMGB) proteins of Plasmodium falciparum:: DNA binding proteins with pro-inflammatory activity
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DOI：
10.1016/j.parint.2007.11.005
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发表时间：
2008-06-01
影响因子：
1.9
通讯作者：
Chauhan, Virander S.
中科院分区：
文献类型：
--
作者：
Kumar, Krishan;Singal, Ankita;Chauhan, Virander S.
高迁移率组盒染色体蛋白I （HMGB I）是一种丰富的非组蛋白结构染色体蛋白，在不同物种中具有高度保守性。从疟原虫恶性疟原虫中鉴定并克隆了hmgb1的同源物。序列分析表明，恶性疟原虫hmgb1 （pfhmgb1）与酿酒酵母、人和小鼠的HMG盒蛋白同源性分别为45%、23%和18%，PfHMGB2与酿酒酵母、人和小鼠的HMG盒蛋白同源性分别为42%、21%和17%。寄生虫pfhmgb1和PfHMGB2蛋白含有一个类似于哺乳动物HMGB1的B-Box结构域。电泳迁移率转移实验（EMSA）显示重组pfhmgb1和PfHMGB2与DNA结合。使用特异性抗体的免疫荧光分析显示，这些蛋白在环状细胞核中大量表达。在滋养体和分裂体阶段，pfhmgb1和PfHMGB2在寄生细胞质中也存在显著水平。研究发现，pfhmgb1和PfHMGB2都是促炎细胞因子如TNF α的有效诱导剂。用反转录PCR和酶联免疫吸附法对小鼠腹膜巨噬细胞进行分析。这些结果表明，分泌的PfHMGB I和PtHMGB2可能引起/触发与疟疾感染相关的宿主炎症免疫反应。2007爱思唯尔爱尔兰有限公司版权所有。
High mobility group box chromosomal protein I (HMGB I), known as an abundant, non-histone architectural chromosomal protein, is highly conserved across different species. Homologues of HMGB I were identified and cloned from malaria parasite, Plasmodium falciparum. Sequence analyses showed that the P.Falciparum HMGB 1 (PfHMGB 1) exhibits 45, 23 and 18%, while PfHMGB2 shares 42, 21 and 17% homology with Saccharomyces cerevisiae, human and mouse HMG box proteins respectively. Parasite PfHMGB I and PfHMGB2 proteins contain one HMG Box domain similar to B-Box of mammalian HMGB1. Electrophoretic Mobility Shift Assay (EMSA) showed that recombinant PfHMGB 1 and PfHMGB2 bind to DNA. Immunofluorescence Assay using specific antibodies revealed that these proteins are expressed abundantly in the ring stage nuclei. Significant levels of PfHMGB 1 and PfHMGB2 were also present in the parasite cytosol at trophozoite and schizont stages. Both, PfHMGB I and PfHMGB2 were found to be potent inducers of pro-inflammatory cytokines such as TNF alpha. from mouse peritoneal macrophages as analyzed by both reverse transcription PCR and by ELISA. These results suggest that secreted PfHMGB I and PtHMGB2 may be responsible for eliciting/ triggering host inflammatory immune responses associated with malaria infection. (c) 2007 Elsevier Ireland Ltd. All rights reserved.