Induction of lysosomal phospholipase A2 through the retinoid X receptor in THP-1 cells
Induction of lysosomal phospholipase A2 through the retinoid X receptor in THP-1 cells
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DOI：
10.1194/jlr.m300342-jlr200
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发表时间：
2004-04-01
影响因子：
6.5
通讯作者：
Shayman, JA
中科院分区：
文献类型：
--
作者：
Abe, A;Poucher, HK;Shayman, JA
酸性磷脂酶A（2）（LPLA（2））是近年来分离纯化并克隆的一种酶。THP-1细胞用于表征LPLA 2的基因诱导。用几种分化剂刺激THP-1细胞。在用佛波酯处理的细胞中，LPLA（2）mRNA和活性增加，但用维生素D3、干扰素-γ或粒细胞巨噬细胞集落刺激因子处理的细胞中则没有。全反式维甲酸以剂量和时间依赖性方式增强mRNA表达和酶活性。维甲酸的天然9-顺式和13-顺式异构体增强转录和活性。两类核受体，视黄酸受体（RAR）和类维生素A X受体（RXR），介导视黄酸信号传导。特异性RAR和RXR激动剂用于鉴定负责视黄酸诱导LPLA（2）的核受体。用RAR激动剂4-[E-2-四氢-5，5，8，8-四甲基-2-萘基] I-丙烯基苯甲酸（TTNPB）处理导致LPLA的mRNA表达和活性小幅且具有统计学显著性的增加（2）。RXR激动剂甲氧普烯酸与全反式视黄酸一样，在增加mRNA和酶活性方面发挥作用。甲氧普烯酸和TTNPB的效果没有协同作用。过氧化物酶体增殖物激活受体γ激动剂15-脱氧-δ（12，14）-前列腺素J（2）和曲格列酮不能诱导LPLA（2）活性和mRNA。因此，在THP-1细胞中，RXR依赖性途径控制视黄酸对LPLA（2）基因的激活。
An acidic phospholipase A(2) (LPLA(2)) 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 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-bans-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] I-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-tram-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.