Benzo(a)pyrene inhibits expression of inducible heat shock protein 70 in vascular endothelial cells.
Benzo(a)pyrene (BaP), a ubiquitous environmental pollutant known to cause many diseases including atherosclerosis, induces a dose-dependent reduction in the levels of the inducible Hsp70. To explore the mechanism underlying the reduction of Hsp70, we measured the levels of Hsp70, cytoplasmic and nuclear heat shock factor 1 (HSF1) in porcine aortic endothelial cells using Western blot, and then further characterized the binding ability of HSF1 and heat shock element (HSE) by electrophoretic mobility shift assay. We found that when porcine aortic endothelial cells were treated by 0.1-10 microM of BaP for 24 h, there was a significant reduction of Hsp70, cytoplasmic and nuclear HSF1 and the binding rate of HSF1 and HSE at 5, 10 microM of BaP but less effective at lower concentrations. The effect of BaP on the Hsp70 expression level was markedly attenuated by co-treatment with phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC). Staurosporine (STP), an inhibitor of PKC, blocked the effect of PMA treatment in combination with BaP. These results suggest that BaP might inhibit Hsp70 levels by reducing the expression of HSF1 and decreasing binding of HSF1 and HSE via PKC-dependent signaling pathways that might be involved in the regulation of Hsp70 gene expression under BaP.
Gong
Z
Z
Department of Occupational and Environmental Health and Ministry of Education Key Lab for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
Yang
J
J
Yang
M
M
Wang
F
F
Wei
Q
Q
Tanguay
R M
RM
Wu
T
T
D000818:Animals; D001564:Benzo(a)pyrene / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D024202:Electrophoretic Mobility Shift Assay; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D020536:Enzyme Activators / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019311:Staurosporine / Q000494:pharmacology; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger; D001564:Benzo(a)pyrene; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate