TY - JOUR
T1 - Benzo(a)pyrene inhibits expression of inducible heat shock protein 70 in vascular endothelial cells
AU - Gong, Z.
AU - Yang, J.
AU - Yang, M.
AU - Wang, F.
AU - Wei, Q.
AU - Tanguay, R. M.
AU - Wu, T.
N1 - Funding Information:
This work was supported by research funds from the National Nature Science Foundation of China (NNSFC, 30371204 and 30525031), from the National Key Basic Research and Development Program of China (2002CB512905) and from the NNSFC of China and the Canadian Institute of Health Research of Canada for a research exchange program. The authors declare they have no competing financial interests.
PY - 2006/10/25
Y1 - 2006/10/25
N2 - 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 μM 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 μM 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.
AB - 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 μM 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 μM 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.
KW - Benzo(a)pyrene
KW - Inducible heat shock protein 70
KW - Vascular endothelial cell
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U2 - 10.1016/j.toxlet.2006.07.307
DO - 10.1016/j.toxlet.2006.07.307
M3 - Article
C2 - 16962263
AN - SCOPUS:33748935380
SN - 0378-4274
VL - 166
SP - 229
EP - 236
JO - Toxicology Letters
JF - Toxicology Letters
IS - 3
ER -