Interaction between AhR and HIF-1 signaling pathways mediated by ARNT/HIF-1β

Abstract

Background The main causes of lung cancer are smoking, environmental pollution and genetic susceptibility. It is an indisputable fact that PAHs are related to lung cancer, and benzo(a) pyrene is a representative of PAHs. The purpose of the current investigation was to investigate the interaction between AhR and HIF-1 signaling pathways in A549 cells, which provide some experimental basis for scientists to find drugs that block AhR and HIF-1 signaling pathway to prevent and treat cancer. Methods This project adopts the CYP1A1 signaling pathways and the expression of CYP1B1 is expressed as a measure of AhR strength index. The expression of VEGF and CAIX volume as a measure of the strength of the signal path HIF-1 indicators. Through the construction of plasmid vector, fluorescence resonance energy transfer, real-time quantitative PCR, western blotting and immunoprecipitation, the interaction between AhR signaling pathway and HIF-1 signaling pathway was observed. Results BaP can enhance the binding ability of HIF-1α protein to HIF-1β/ARNT in a dose-dependent manner without CoCl2. However, the binding ability of AhR protein to HIF-1β/ARNT is inhibited by HIF-1α signaling pathway in a dose-dependent manner with CoCl2. Conclusion It is shown that activation of the AhR signaling pathway does not inhibit the HIF-1α signaling pathway, but activation of the HIF-1α signaling pathway inhibits the AhR signaling pathway.

Naringenin protects against acute pancreatitis-associated intestinal injury by inhibiting NLRP3 inflammasome activation via AhR signaling

“…Generally, AhR is considered a part of the basic helix-loop-helix/Per-Arnt-Sim superfamily and bound to several cochaperones in an inactive form in the cytosol (Wang et al, 2018). After ligand binding, the cochaperones release AhR, which is then carried into the nucleus, where it heterodimerizes with the nuclear translocator of the aryl hydrocarbon receptor (ARNT) (Neavin et al, 2018;Modoux et al, 2022;Zhang et al, 2022). According to previous research, AhR is a possible target for treating disorders with uncontrolled inflammasome activation because it inhibits the transcription of the NLRP3 inflammasome as a negative regulator of NLRP3 inflammasome activity (Huai et al, 2014).…”

Anti-PD-L1 therapy altered inflammation but not survival in a lethal murine hepatitis virus-1 pneumonia model

“…These were Ahr (aryl hydrocarbon receptor), Ca13 (carbonic anhydrase 13), Epo (erythropoietin), Igsf3 (immunoglobulin superfamily member 3), IL-1a (interleukin 1a), Tnfrsf12a [tumor necrosis factor (TNF) ligand superfamily member 12 also known as TNF-related weak inducer of apoptosis (TWEAK)], Crim1 (cysteine-rich motor neuron 1), and Tnr (tenascin-R). These shifts in virally induced serum proteins may reflect responses to hypoxia [Epo ( 35 ), IL-1a ( 36 ), Ahr ( 37 )], changes in angiogenesis [Crim1 ( 38 ), Tnfrsf12a ( 39 )], inflammation [Ahr ( 40 ), IL-1a ( 36 ), Tnfrsf12a ( 39 )], or cell adhesion [Tnfrs12a and Igsf3 ( 41 )], and additional responses not yet fully explored [Ca13 ( 42 )].…”

The Garlic Compound, Diallyl Trisulfide, Attenuates Benzo[a]Pyrene-Induced Precancerous Effect through Its Antioxidant Effect, AhR Inhibition, and Increased DNA Repair in Human Breast Epithelial Cells

“…AhR forms a heterodimer complex (AhR/ARNT) by binding to the xenobiotic responsive elements (XRE), where transcription is initiated in conjunction with the hypoxia-responsive elements (HRE) [ 40 ]. B[a]P is a main ligand of AhR that directly binds to the receptor and induces its biological effects associated with carcinogenesis in cancer and the development and progression of breast cancer [ 41 , 42 ]. In this study, AhR expression was significantly ( p < 0.0001) induced following 24 h exposure to 1 μM B[a]P. The CoTx significantly decreased ( p < 0.0001) the AhR response at the same time point, thus attenuating the AhR expression in B[a]P-treated breast epithelial cells.…”

“…The expression of cytochrome P450 enzymes, such as CYP1A1, is a signature hallmark of AhR signal transmission activation and metabolism [ 41 ]. CYP1A1 is a major enzyme that plays a role in carcinogenesis and tumor progression by inducing AhR by binding environmental pollutants such as B[a]P and inhaling chemicals that mitigate their biological and toxic effects [ 44 ].…”