Toward elucidation of dioxin-mediated chloracne and Ah receptor functions

Biochemical Pharmacology
Karl Walter Bock

Abstract

Target cells and molecular targets responsible for dioxin-mediated chloracne, the hallmark of dioxin toxicity, are reviewed. The dioxin TCDD accumulates in sebum, and thereby persistently activates the Ah receptor (AhR), expressed in bipotential stem/progenitor cells of the sebaceous gland. AhR operates in cooperation with other transcription factors including c-Myc, Blimp1 and ß-Catenin/TCF: c-Myc stimulates exit of stem cells from quiescence to proliferating sebocyte progenitors; Blimp1 is a major c-Myc repressor, and ß-Catenin/TCF represses sebaceous gland differentiation and stimulates differentiation to interfollicular epidermis. TCDD has been demonstrated to induce Blimp1 expression in the sebocyte stem/progenitor cell line SZ95, leading to sebocyte apoptosis and proliferation of interfollicular epidermis cells. These findings explain observations in TCDD-poisoned individuals, and identify target cells and molecular targets of dioxin-mediated chloracne. They clearly demonstrate that the AhR operates in a cell context-dependent manner, and provide hints to homeostatic functions of AhR in stem/progenitor cells.

References

Apr 11, 1991·Journal of Toxicology and Environmental Health·P MocarelliV Carreri
Jun 1, 1985·Scandinavian Journal of Work, Environment & Health·R R Suskind
Feb 26, 2000·Science·F M Watt, B L Hogan
Jun 3, 2000·Annual Review of Pharmacology and Toxicology·Y Z GuC A Bradfield
Jan 24, 2002·The Journal of Biological Chemistry·Rosalie C Sears, Joseph R Nevins
Oct 8, 2005·Journal of Cellular Biochemistry·Jennifer L Marlowe, Alvaro Puga
Mar 21, 2006·Biochemical Pharmacology·Karl Walter Bock, Christoph Köhle
Dec 14, 2007·Chemical Research in Toxicology·Linh P Nguyen, Christopher A Bradfield
Jan 15, 2008·American Journal of Epidemiology·Dario ConsonniPier Alberto Bertazzi
Jan 26, 2008·The Journal of Investigative Dermatology·George GaitanisAlexios-Leandros Skaltsounis
Nov 26, 2008·Biochemical Pharmacology·Kristen A Mitchell, Cornelis J Elferink
Feb 25, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Albert BraeuningMichael Schwarz
Dec 1, 2009·The International Journal of Biochemistry & Cell Biology·Marlon R Schneider, Ralf Paus
Mar 25, 2014·Annual Review of Immunology·Brigitta StockingerJoão H Duarte
May 20, 2014·Biochemical Pharmacology·Karl Walter Bock

❮ Previous
Next ❯

Citations

Jul 2, 2016·Reviews in Endocrine & Metabolic Disorders·Qiang Ju, Christos C Zouboulis
Dec 17, 2016·Experimental Animals·Kaname Kawajiri, Yoshiaki Fujii-Kuriyama
Oct 4, 2017·Toxicological Sciences : an Official Journal of the Society of Toxicology·Fabienne FontaoOlivier Sorg
Apr 13, 2019·Acta Neuropathologica·Isaac N PessahSharon K Sagiv
Feb 9, 2020·International Journal of Molecular Sciences·Carolyn Klocke, Pamela J Lein
Nov 20, 2018·EFSA Journal·UNKNOWN EFSA Panel on Contaminants in the Food Chain (CONTAM)Laurentius Ron Hoogenboom
Mar 2, 2021·World Journal of Clinical Cases·Yan MaWen-Li Feng

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis