Curcumin suppresses the transformation of an aryl hydrocarbon receptor through its phosphorylation.
Halogenated and polycyclic aromatic hydrocarbons induce diverse biochemical responses through the transformation of a cytosolic aryl hydrocarbon receptor (AhR). In mouse hepatoma Hepa-1c1c7 cells, curcumin, a yellow pigment of Curcuma longa, did not inhibit the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced translocation of the AhR into the nucleus, but rather accelerated it. In the nucleus, curcumin inhibited the TCDD-induced heterodimerization of the AhR with an AhR nuclear translocator (Arnt), an essential partner for the transformation, and also dose-dependently inhibited the TCDD-evoked phosphorylation of both the AhR and Arnt. Moreover, curcumin significantly inhibited the TCDD-induced activation of protein kinase C (PKC), which is involved in the transformation, decreased the TCDD-induced DNA-binding activity of the AhR/Arnt heterodimer, and downregulated CYP1A1 expression. In a cell-free system, curcumin inhibited the binding of 3-methylcholanthrene, an AhR agonist, to the receptor. These results indicate that curcumin is able to bind to the AhR as a ligand, but suppresses its transformation by inhibiting the phosphorylation of AhR and Arnt, probably by PKC.
Nishiumi
Shin
S
Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo, Japan.
Yoshida
Ken-Ichi
K
Ashida
Hitoshi
H
D021581:Active Transport, Cell Nucleus; D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004785:Environmental Pollutants / Q000494:pharmacology; D004789:Enzyme Activation; D066298:In Vitro Techniques; D008748:Methylcholanthrene / Q000494:pharmacology; D051379:Mice; D010766:Phosphorylation; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*
C497397:Arnt protein, mouse; D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D008748:Methylcholanthrene; D019363:Cytochrome P-450 CYP1A1; D011493:Protein Kinase C; D003474:Curcumin