title: Aryl hydrocarbon receptor-mediated induction of the cytosolic phospholipase A(2)alpha gene by 2,3,7,8-tetrachlorodibenzo-p-dioxin in mouse hepatoma Hepa-1c1c7 cells.
abstract: 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(2)s (PLA(2)s) 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(2)alpha (cPLA(2)alpha), 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.
authors.affiliation: Department of Agrobioscience, Kobe University, Rokkodai, Nada-ku, Hyogo, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kinehara
authors.forename: Itsuko
authors.initials: I
authors.lastname: Fukuda
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Yoshida
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ashida
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000201:enzymology; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D003600:Cytosol / Q000201:enzymology; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D054513:Group IV Phospholipases A2 / Q000235:genetics* / Q000378:metabolism; D007438:Introns / Q000235:genetics; D008113:Liver Neoplasms / Q000201:enzymology; D051379:Mice; D008856:Microscopy, Fluorescence; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D017931:DNA Primers; D004273:DNA, Neoplasm; D018336:Receptors, Aryl Hydrocarbon; D054513:Group IV Phospholipases A2