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Originally published In Press as doi:10.1194/jlr.M300342-JLR200 on February 1, 2004
Journal of Lipid Research, Vol. 45, 667-673, April 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology
Induction of lysosomal phospholipase A2 through the retinoid X receptor in THP-1 cells
Akira Abe,
Heather K. Poucher,
Miki Hiraoka and
James A. Shayman1
Nephrology Division, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109
1 To whom correspondence should be addressed. e-mail: jshayman{at}umich.edu
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- , 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 agonists 15-deoxy- 12,14-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.
Supplementary key words retinoic acid lysosome phospholipase phorbol ester

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Copyright © 2004 by the American Society for Biochemistry and Molecular Biology.
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