Independent arachidonic acid-mediated gene regulatory pathways in lymphocytes.
In the BW5147 T cell line, we have identified two independent regulatory pathways by which arachidonic acid (20:4) can alter gene expression. The inhibitory effect of 20:4 upon stearoyl-CoA desaturase 2 (SCD2) gene expression was seen to be independent of oxidation of 20:4 by either the lipoxygenase or cyclooxygenase pathways. Moreover, oxidized metabolites of 20:4 (15-HPETE and 15-HETE) failed to diminish SCD2 mRNA accumulation whereas 20:4 itself was effective in completely suppressing SCD2 gene expression. In contrast, the transcriptional induction of the proto-oncogene c-fos was dependent upon the oxidation of 20:4 by the lipoxygenase pathway. By using the protein synthesis inhibitor, cycloheximide, we also show that the 20:4-mediated regulatory effects upon SCD2 or c-fos are completely independent of new protein synthesis. Collectively, the results identify the existence of multiple, independent, intracellular 20:4-mediated regulatory pathways operating simultaneously within this cell type.
Tebbey
P W
PW
Dept. of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, NC 27858-4354.
Buttke
T M
TM
D000199:Actins / Q000096:biosynthesis; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D015152:Blotting, Northern; D002467:Cell Nucleus; D003513:Cycloheximide / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016762:Genes, fos; D016758:Genes, jun; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology; D015289:Leukotrienes / Q000494:pharmacology; D008054:Lipid Peroxides / Q000494:pharmacology; D008223:Lymphoma; D009637:Masoprocol / Q000494:pharmacology; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis*; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D013230:Stearoyl-CoA Desaturase / Q000096:biosynthesis; D013601:T-Lymphocytes; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D000199:Actins; D006893:Hydroxyeicosatetraenoic Acids; D015289:Leukotrienes; D008054:Lipid Peroxides; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016718:Arachidonic Acid; D000431:Ethanol; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D009637:Masoprocol; D003513:Cycloheximide; D013230:Stearoyl-CoA Desaturase; D013755:Tetradecanoylphorbol Acetate