Comparative study of p38 MAPK signal transduction pathway of peripheral blood mononuclear cells from patients with coal-combustion-type fluorosis with and without high hair selenium levels

Comparative study of p38 MAPK signal transduction pathway of peripheral blood mononuclear cells from patients with coal-combustion-type fluorosis with and without high hair selenium levels
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高发硒与非高发硒燃煤型氟中毒患者外周血单个核细胞p38 MAPK信号转导通路的比较研究

DOI:
10.1016/j.ijheh.2010.06.002
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发表时间:
2010-09-01
影响因子:
6
通讯作者:
Liu, Zhengwen
Liu, Zhengwen
中科院分区:
医学2区
文献类型:
--
作者:
Chen, Qun;Wang, Zhilun;Liu, Zhengwen

文献摘要

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燃煤型氟中毒仅在国内有报道,其发病机制尚未完全阐明。氟化物会引起慢性毒性作用,而硒则通过人体细胞中的信号转导来调节细胞活动。本研究纳入了三组血清、尿氟和发硒明确的受试者:高氟+高硒组、高氟组和正常对照组。分别采用Western blotting和定量实时RT-PCR测定外周血单核细胞(PBMC)中p38、NF-kappa B p65、caspase-3和p53基因在蛋白和mRNA水平的表达。结果显示,高氟组p38、NF-κB p65、caspase-3蛋白表达量高于其他两组。高氟+高硒组NF-κB p65和caspase-3 mRNA水平显着高于对照组,低于高氟组。高氟+高硒组p53 mRNA和蛋白水平显着高于其他两组。这些结果表明,硒可能影响燃煤型氟中毒患者PBMCs中p38信号转导通路相关蛋白和基因的表达,并上调p53的表达。 (C) 2010 爱思唯尔有限公司。版权所有。
Coal-combustion-type fluorosis has only been reported in China and its pathogenesis has not been fully understood. Fluoride causes chronic toxic effects and selenium modulates cellular activities through signal transduction in human cells. The present study enrolled three groups of subjects with well-defined serum and urine fluoride and hair selenium: high fluoride + high selenium group, high fluoride group and normal control group. The expressions of p38, NF-kappa B p65, caspase-3 and p53 genes at both protein and mRNA levels in peripheral blood mononuclear cells (PBMCs) were determined by Western blotting and quantitative real-time RT-PCR, respectively. The results showed that the expressions of p38, NF-kappa B p65, and caspase-3 protein in high fluoride group were higher than those in the other two groups. The mRNA level of NF-kappa B p65 and caspase-3 was significantly higher in high fluoride + high selenium group than control and lower than high fluoride group. The mRNA and protein level of p53 was significantly higher in high fluoride + high selenium group than that in other two groups. These results suggest that selenium may influence the protein and gene expression associated with p38 signal transduction pathway and up-regulate p53 expression in PBMCs from patients with coal-combustion-type fluorosis. (C) 2010 Elsevier GmbH. All rights reserved.