出版社：American Society for Biochemistry and Molecular Biology
摘要：An acidic phospholipase A2 (LPLA2) was recently purified and cloned. THP-1 cells were used to characterize the gene induction of LPLA2. THP-1 cells were stimulated with several differentiation agents. The LPLA2 mRNA and activity increased in cells treated with phorbol ester but not with vitamin D3, interferon-γ, or granulocyte macrophage colony-stimulating factor. All- trans -retinoic acid enhanced mRNA expression and enzyme activity in a dose- and time-dependent manner. The natural 9- cis and 13- cis isomers of retinoic acid enhanced transcription and activity. Two classes of nuclear receptors, the retinoic acid receptor (RAR) and the retinoid X receptor (RXR), mediate retinoic acid signaling. Specific RAR and RXR agonists were used to identify the nuclear receptor responsible for LPLA2 induction by retinoic acid. Treatment with the RAR agonist 4-[E-2-tetrahydro-5,5,8,8-tetra-methyl-2-naphthalenyl]1-propenyl benzoic acid (TTNPB) resulted in a small and statistically significant increase of the mRNA expression and activity of LPLA2. The RXR agonist methoprene acid worked as well as all- trans -retinoic acid at increasing both mRNA and enzyme activity. The methoprene acid and TTNPB effects were not synergistic. The peroxisome proliferator-activated receptor γ agonists 15-deoxy-Δ12,14-prostaglandin J2 and troglitazone failed to induce LPLA2 activity and mRNA. Thus, an RXR-dependent pathway controls LPLA2 gene activation by retinoic acid in THP-1 cells.
