ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of mitogen activated protein kinase (MAPK) signal transduction pathways on heat shock protein 70 (HSP70) gene expression in endothelial cells exposed to benzo(a)pryene (BaP).</p><p><b>METHODS</b>Porcine aortic endothelial cells were pre-treated or by PD98059 (10 micro mol/L) or SB203580 (20 micro mol/L) for 1 hour, then treated with different concentrations of BaP (0, 0.1, 0.5, 1.0, 5.0 and 10.0 micro mol/L) for 24 hours respectively;Expression levels of three phosphorylated MAPKs [extracellular signal regulated protein kinase (ERK), c-Jun amino-terminal kinase (JNK), and p38] and HSP70 were determined by Western-blot.</p><p><b>RESULTS</b>The three phosphorylated MAPKs expressional levels especially p-ERK1 had different extents of changes with dose-response relationship under BaP exposure. BaP inhibited the expression of HSP70, which significantly decreased in medium and high dose group (>or= 1.0 micro mol/L) but did not decrease in control group (P < 0.05). Although the inhibitor of ERK (PD98059) could partly weaken the inhibited effects of BaP on HSP70 expression, HSP70 expression levels of endothelial cells pre-treated with PD98059 were still significantly lower than that of control cells (P < 0.05).</p><p><b>CONCLUSION</b>ERK1 pathway might play some roles in HSP70 gene expression in endothelial cells exposed to BaP, and other unknown signal pathways might also have some effects on this process.</p>
Subject(s)
Animals , Benzo(a)pyrene , Toxicity , Blotting, Western , Dose-Response Relationship, Drug , Endothelial Cells , Metabolism , Enzyme Inhibitors , Pharmacology , Flavonoids , Pharmacology , HSP70 Heat-Shock Proteins , Imidazoles , Pharmacology , JNK Mitogen-Activated Protein Kinases , MAP Kinase Kinase 4 , Mitogen-Activated Protein Kinase Kinases , Mitogen-Activated Protein Kinases , Pyridines , Pharmacology , Signal Transduction , Physiology , Swine , p38 Mitogen-Activated Protein KinasesABSTRACT
<p><b>OBJECTIVE</b>To explore the effect of benzo(a)pyrene (BaP) on the expression and the activities of cytochrome P450 1A1 (CYP1A1) of porcine aortic endothelial cells.</p><p><b>METHODS</b>Porcine aortic endothelial cells were cultured in vitro, and treated with different concentrations of BaP (0, 0.5, 1.0, 5.0, 10.0 micro mol/L) for 24 hours, CYP1A1 expression was determined by Western blot and immunohistochemistry. At the same time, the ethoxyresorufin-o-deethylase (EROD) activities were measured by spectrofluorometer.</p><p><b>RESULTS</b>By Western blot, the expression of CYP1A1 of control cells was not found, but the expression of CYP1A1 of cells treated with BaP was found; By immunohistochemistry, only part of endothelial cells treated with BaP had positive expression of CYP1A1. The peak activities of EROD induced by BaP was at the concentration of 0.5 - 1.0 micro mol/L.</p><p><b>CONCLUSION</b>BaP could induce part of endothelial cells to synthesize CYP1A1. BaP of 0.5 - 1.0 micro mol/L could induce peak activities of EROD.</p>