The Role of Aryl Hydrocarbon Receptor Activation in Circadian Regulation
Circadian rhythms are important near-24-hour cycles that regulate multiple processes in living organisms. These rhythms are generated by clock genes that oscillate in the suprachiasmatic nucleus (SCN) of the basal hypothalamus. Environmental contaminants, such as the prototypical dioxins, potentially disrupt circadian rhythms through actions mediated by the Aryl hydrocarbon receptor (AhR), a protein that is structurally similar to the core clock genes. A photoproduct of tryptophan, 6-formylindolo [3,2-b]carbazole (FICZ), is a potent endogenous AhR ligand and may act as a potential factor in regulating circadian rhythm. To examine whether AhR activation occurs in the master clock by light-activated tryptophan, we used SCN 2.2, rat immortalized SCN cells, and identified changes in CYP1A1, per1 and c-fos mRNA expression. The results of these experiments suggest that the AhR signaling pathway is activated by tryptophan photoproducts since the relative amounts of RNA for cyp1a1 and c-fos (known AhR targets) were increased. Also, the results for these two genes showed statistical significance when comparing both genes with their respective control groups. In addition, the statistical results suggested that the AhR receptor is implicated in circadian rhythmicity. AhR seems to suppress the expression of Per1 in the SCN cells. This hypothesis might be tested by incubating the SCN 2.2 cells with tryptophan photoproducts for more than three hours and looking at the cells' behavior at different times over an interval of more than one circadian cycle.
School:
University of Puerto Rico at Bayamón
Department:
Human Biology
Research Advisor:
Shelley Tischkau
Department of Research Advisor:
Veterinary Biosciences
Year of Publication:
2006