Differential effects of polycyclic aromatic hydrocarbons on transactivation of AP‐1 and NF‐κB in mouse epidermal cl41 cells

Abstract

Polycyclic aromatic hydrocarbons (PAHs) and their derivatives, such as benzo[a]pyrene (B[a]P), (+/-)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (B[a]PDE), and 5-methylchrysene-1,2-diol-3,4-epoxide (5-MCDE), are complete carcinogens. However, the tumor promotion effects of PAHs remain unclear. We therefore investigated the possible activation of activator protein-1 (AP-1) and nuclear factor-kappaB (NFkappaB) in mouse epidermal Cl41 cells after different PAHs treatments, including B[a]P, B[a]PDE, chrysene-1,2-diol-3,4-epoxid (CDE), and 5-MCDE. The results showed that B[a]PDE and 5-MCDE were able to activate AP-1 and NF-kappaB, whereas B[a]P showed only marginal effect on AP-1 activation, and B[a]P and CDE had no effect on NF-kappaB activation. Treatment with either B[a]PDE or 5-MCDE also resulted in mitogen-activated protein kinases (MAPKs) activation as well as inhibitory subunit kappa-B (IkappaBalpha) phosphorylation and degradation, whereas B[a]P and CDE had no effect. Pretreatment with PD98059, a specific inhibitor for extracellular signal-regulated protein kinases (ERKs) upstream kinase MEK1/2, or SB202190, a p38 kinase inhibitor, resulted in a dramatic inhibition of B[a]PDE-induced AP-1 transactivation. In addition, B[a]PDE-induced AP-1 activation was also inhibited by overexpressing a dominant negative mutant of JNK1 in the cells. All these suggest ERKs, c-jun N-terminal kinases (JNKs), and p38 kinase signal transduction pathways are required for AP-1 induction by B[a]PDE. Taken together, B[a]PDE and 5-MCDE are the active compounds of PAHs to initiate signaling pathways. Considering the important roles of AP-1 and NF-kappaB in tumor promotion, we speculated the activation of AP-1 and NF-kappaB by B[a]PDE and 5-MCDE may involve in their or their parent compounds' tumor promotion effects. This study may help in better understanding the tumor promotion effects of PAHs.

Particulate Matter Disrupts Human Lung Endothelial Barrier Integrity via ROS- and p38 MAPK–Dependent Pathways

“…Our finding that PM selectively activates p38 MAPK b provided a novel approach to potentially define differential biochemical functions of p38 MAPK a and p38 MAPK b. In this regard, prior reports indicate that the chrysene component in PM stimulate MAPK activation (32) with benzopyrene-7,8-diol-9,10-epoxide (BPDE) as well as chrysene-1,2-diol-3,4-epoxide, common components in particulate air pollution, rapidly activate p38 MAPK and JNK (33). Further interrogation of the specific PM component or cellular factor that selectively activates p38 MAPK b may provide novel insights into p38 MAPK b activities in endothelial cells.…”

Coordination of JNK1 and JNK2 Is Critical for GADD45α Induction and Its Mediated Cell Apoptosis in Arsenite Responses

“…After exposure to arsenite for various doses and time periods as indicated in the figure legends, the cells were washed once with ice-cold phosphate-buffered saline and collected with SDS-sample buffer (22). The cell extracts were sonicated, denatured by heating at 100°C for 5 min, and quantified with a Dc protein assay kit (Bio-Rad).…”

A JNK1/AP-1–Dependent, COX-2 Induction Is Implicated in 12-O-Tetradecanoylphorbol-13-Acetate–Induced Cell Transformation through Regulating Cell Cycle Progression

“…After exposure to TPA for various times as indicated in the figure legends, the cells were washed once with ice-cold PBS and collected with SDS-sample buffer (58). The cell extracts were sonicated, denatured by heating at 100jC for 5 min, and quantified with a detergentcompatible protein assay kit (Bio-Rad).…”