Abstract
An acidic phospholipase A(2) (LPLA(2)) was recently purified and cloned. THP-1 cells were used to characterize the gene induction of LPLA(2). THP-1 cells were stimulated with several differentiation agents. The LPLA(2) mRNA and activity increased in cells treated with phorbol ester but not with vitamin D3, interferon-gamma, 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 LPLA(2) 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 LPLA(2). 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 gamma agonists 15-deoxy-Delta(12,14)-prostaglandin J(2) and troglitazone failed to induce LPLA(2) activity and mRNA. Thus, an RXR-dependent pathway controls LPLA(2) gene activation by retinoic acid in THP-1 cells.
Highlights
An acidic phospholipase A2 (LPLA2) was recently purified and cloned
It is reported that all-trans-retinoic acid (ATRA) is able to induce lysosomal phospholipase A2 (LPLA2) mRNA and enzyme activity in THP-1 cells and that the induction is through a retinoid X receptor (RXR)-dependent pathway, which is independent of retinoic acid receptor (RAR) or peroxisome proliferator-activated receptor ␥ (PPAR␥)
LPLA2 and GAPDH mRNAs were detected by RT-PCR, and the enzyme activity in the soluble fraction was determined by its transacylase activity
Summary
An acidic phospholipase A2 (LPLA2) was recently purified and cloned. THP-1 cells were used to characterize the gene induction of LPLA2. Specific RAR and RXR agonists were used to identify the nuclear receptor responsible for LPLA2 induction by retinoic acid. The RXR agonist methoprene acid worked as well as all-trans-retinoic acid at increasing both mRNA and enzyme activity.
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