Aryl hydrocarbon receptor-mediated induction of the cytosolic phospholipase A_2α gene by 2,3,7,8-tetrachlorodibenzo-p-dioxin in mouse hepatoma Hepa-1c1c7 cells(GENETICS, MOLECULAR BIOLOGY, AND GENE ENGINEERING)

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Upon binding to ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an aryl hydrocarbon receptor (AhR) is activated to form a heterodimer with an aryl hydrocarbon receptor nuclear translocator (Arnt). This complex binds to DNA. It has been shown that the AhR bonds to a DNA sequence called the dioxin response element (DRE), which controls the expression of battery genes. It is reported that TCDD releases arachidonic acid from membrane phospholipids via activation of phospholipase A_2s (PLA_2s) in various cell types. Recently, we demonstrated that the TCDD-activated AhR binds to the second intron of the Pla2g4a gene, which encodes cytosolic phospholipase A_2α (cPLA_2α), in mouse hepatoma Hepa-1c1c7 cells. This result suggests that Pla2g4a appears to be a target gene of the AhR. In the present study, we investigated whether the transcriptional regulation of Pla2g4a is dependent on the AhR in Hepa-1c1c7 cells. Treatment of the cells with TCDD increased mRNA expression of Pla2g4a and enzymatic activity of PLA_2, while this increased expression was not observed in AhR-defective c12 cells. After transient transfection of an Ahr gene-expressing plasmid into the c12 cells, expression of Pla2g4a was increased by TCDD. These results indicate that Pla2g4a may be a novel target gene of the AhR, and its transcriptional induction is mediated through binding of the AhR to the second intron of Pla2g4a, although this target site does not have a typical DRE sequence.

Aryl hydrocarbon receptor-mediated induction of the cytosolic phospholipase A_2α gene by 2,3,7,8-tetrachlorodibenzo-p-dioxin in mouse hepatoma Hepa-1c1c7 cells(GENETICS, MOLECULAR BIOLOGY, AND GENE ENGINEERING)

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