Dioxin toxicity, aryl hydrocarbon receptor signaling, and apoptosis—Persistent pollutants affect programmed cell death

Abstract

Exogenous ligands of the aryl hydrocarbon receptor (AhR) such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related substances are highly toxic pollutants ubiquitously present in the environment. They cause a variety of toxic effects to different organs and tissues. Among other effects, TCDD exposure to laboratory animals leads to thymus atrophy and immunosuppression on the one hand, and to tumor formation on the other. Apoptosis appears to be involved in both these toxic effects: AhR activation by TCDD was discussed to induce apoptosis of immune cells, leading to the depletion of thymocytes and ultimately immunosuppression. This mechanism could help to explain the highly immunotoxic actions of TCDD but it is nevertheless under debate whether this is the mode of action for immunosuppression by this class of chemical substances. In other cell types, especially liver cells, TCDD inhibits apoptosis induced by genotoxic treatment. In initiation-promotion studies, TCDD was shown to be a potent liver tumor promoter. Among other theories it was hypothesized that TCDD acts as a tumor promoter by preventing initiated cells from undergoing apoptosis. The exact mechanisms of apoptosis inhibition by TCDD are not fully understood, but both in vivo and in vitro studies consistently showed an involvement of the tumor suppressor p53 in this effect. Various strings of evidence have been established linking apoptosis to the detrimental effects of exogenous activation of the AhR. Within this article, studies elucidating the effects of TCDD and related substances on apoptosis signaling, be it inducing or repressing, is to be reviewed.

Activation of the Aryl Hydrocarbon Receptor Leads to Resistance to EGFR TKIs in Non–Small Cell Lung Cancer by Activating Src-mediated Bypass Signaling

“…Activation of AhR signaling upregulates several growth factors, and NSCLC cells require elevated AhR for sustained proliferation (29,30). Moreover, the AhR gene encodes several resistance proteins, drug metabolic enzymes and drug transporters, and it also negatively regulates the rate of apoptosis (31)(32)(33)(34). It is plausible that AhR is implicated in determining the sensitivity of NSCLC to apoptosis-inducing agents, such as targeted therapeutics.…”

Aryl Hydrocarbon Receptor–Dependent Stanniocalcin 2 Induction by Cinnabarinic Acid Provides Cytoprotection against Endoplasmic Reticulum and Oxidative Stress

“…Ligand activation of the AhR results in nuclear translocation of the receptor where it dimerizes with the AhR nuclear translocator (Arnt), or the recently identified binding partner, the Kruppel-like factor 6 (KLF6) (Legraverend et al, 1982;Hankinson, 1993Hankinson, , 1995Wilson et al, 2013). The AhR-Arnt dimer regulates the transcription of numerous drug-metabolizing enzymes, including CYP1A1, by binding to xenobiotic response elements (XREs) located in the target gene promoters (Revel et al, 2003;Marlowe and Puga, 2005;Chopra and Schrenk, 2011). The activated AhR-Arnt complex is subsequently regulated by ubiquitin-mediated proteosomal degradation.…”

The Role of Concentration Ratio of TTiP:AcAc on the Photocatalytic Activity of TiO2 Thin Film in Reducing Degradation Products of Used Frying Oil

“…However, this method need long process and a lot of equipment. The other methods to reduce FFA and PV are the using of acid catalyst [17][18][19] and adding antioxidant [20,21].…”