Nishiumi Shin, Yoshida Ken-Ichi, Ashida Hitoshi
Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo, Japan.
Arch Biochem Biophys. 2007 Oct 15;466(2):267-73. doi: 10.1016/j.abb.2007.08.007. Epub 2007 Aug 22.
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.
卤代芳烃和多环芳烃通过胞质芳烃受体（AhR）的转化诱导多种生化反应。在小鼠肝癌Hepa-1c1c7细胞中，姜黄素（一种姜黄的黄色色素）并不抑制2,3,7,8-四氯二苯并对二恶英（TCDD）诱导的AhR向细胞核的转位，反而加速了这种转位。在细胞核中，姜黄素抑制TCDD诱导的AhR与AhR核转运蛋白（Arnt）的异源二聚化，Arnt是转化过程中的重要伴侣，并且还剂量依赖性地抑制TCDD诱发的AhR和Arnt的磷酸化。此外，姜黄素显著抑制TCDD诱导的蛋白激酶C（PKC）的激活，PKC参与转化过程，降低TCDD诱导的AhR/Arnt异源二聚体的DNA结合活性，并下调CYP1A1表达。在无细胞系统中，姜黄素抑制AhR激动剂3-甲基胆蒽与受体的结合。这些结果表明，姜黄素能够作为配体与AhR结合，但可能通过抑制PKC对AhR和Arnt的磷酸化来抑制其转化。
