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.
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-kB 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-kB p65, and caspase-3 protein in high fluoride group were higher than those in the other two groups. The mRNA level of NF-kB 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.
Chen
Qun
Q
Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Institute of Endemic Diseases, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, People's Republic of China.
Wang
Zhilun
Z
Xiong
Yongmin
Y
Zou
Xiuzhen
X
Liu
Zhengwen
Z
D000328:Adult; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism*; D005260:Female; D005458:Fluoride Poisoning / Q000201:enzymology*; D005459:Fluorides / Q000097:blood / Q000633:toxicity; D006197:Hair / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012643:Selenium / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D051996:Transcription Factor RelA; D016159:Tumor Suppressor Protein p53; D048051:p38 Mitogen-Activated Protein Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D012643:Selenium; D005459:Fluorides