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Activation of p53 as a causal step for atherosclerosis induced by polycyclic aromatic hydrocarbons
Author(s) -
Iwano Shunsuke,
Shibahara Norihito,
Saito Tetsuya,
Kamataki Tetsuya
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.01.009
Subject(s) - liver x receptor , chemistry , phosphorylation , aryl hydrocarbon receptor , metabolite , mutant , retinoid x receptor , dna damage , aryl hydrocarbon receptor nuclear translocator , microbiology and biotechnology , wild type , dna , nuclear receptor , transcription factor , biology , biochemistry , gene
This study was performed to prove our hypothesis that the metabolite(s) of polycyclic aromatic hydrocarbons (PAHs) caused the activation or phosphorylation of p53 via DNA damage to suppress the liver X receptor (LXR)‐mediated signal transductions as a probably more direct mechanism. We found that LXR‐mediated trans ‐activation was inhibited by 3‐methylchoranthrene (MC) and doxorubicin (Dox) in HepG2 cells carrying wild‐type p53, but not in Hep3B cells possessing mutant p53. The exogenous expression of wild‐type p53 suppressed the LXR‐mediated trans ‐activation in Hep3B cells. The expression of mRNA for ATP binding cassette A1 was suppressed by MC and Dox in HepG2 cells. The protein expression of retinoid X receptor (RXR), a partner of LXR to form a heterodimer, was suppressed by MC and Dox in HepG2 cells.