Evidence supporting the hypothesis that one of the main functions of the aryl hydrocarbon receptor is mediation of cell stress responses.
We have previously proposed that one of the major consequences of activation of the aryl hydrocarbon receptor (AhR) by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) could be elicitation of 'cell stress response' reactions [Matsumura, Biochem. Pharmacol. 66 (2003), 527-540]. This hypothesis was based mainly on the similarity between the toxic symptoms, particularly those related to the wasting syndrome, and those induced by bacterial endotoxins, namely lipopolysaccharides (LPS) in vivo, as well as the biochemical and molecular consequences of their toxic actions in vitro. Since the basic action mechanism of LPS as an inducer of cell stress responses (CSR) is known to some extent, including knowledge of their specific receptors (i.e., toll-like receptors) and their signaling process through the inflammatory response messengers, the above comparison offered a good point of reference to this subject. Furthermore, the process of constructing this hypothesis itself has provided us with a good opportunity to give a fresh view on the toxic action patterns of TCDD.
Matsumura
Fumio
F
Department of Environmental Toxicology, University of California, One Shields Avenue, Davis, CA 95616, USA. fmatsumura@ucdavis.edu
Vogel
Christoph F A
CF
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects
D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon