15-deoxy-Δ12,14-prostaglandin J2-induced apoptosis in amnion-like WISH cells
15-deoxy-Δ12,14-prostaglandin J2-induced apoptosis in amnion-like WISH cells
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DOI：
10.1016/s0090-6980(01)00164-2
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发表时间：
2001-12-01
影响因子：
2.9
通讯作者：
Gilmour, RS
中科院分区：
文献类型：
--
作者：
Keelan, JA;Helliwell, RJA;Gilmour, RS
破裂部位的细胞凋亡已被认为在胎膜早破中起作用，胎膜早破是一种与新生儿败血症和早产风险增加相关的疾病。我们研究了过氧化物酶体增殖物激活受体（PPAR）-γ配体15-脱氧-Delta（12，14）PGJ（2）（15 d-PGJ（2））、Delta（12）PGJ 2（，）西格列酮和罗格列酮诱导WISH细胞系凋亡的能力。15 d-PGJ（2）（10 μ M）在2小时内诱导细胞凋亡的形态学特征，随后不久出现生化指标（半胱天冬酶活化和底物裂解）; 16小时观察到最大细胞死亡（约60%），EC 50约为7 μ M 15 d-PGJ（2）。Delta（12）-PGJ（2）也诱导细胞凋亡，但效力较低，作用速度也慢得多。而环格列酮也诱导细胞凋亡，罗格列酮对细胞活力没有影响。15 d-PGJ（2）和Delta（12）PGJ（2）诱导细胞凋亡的机制可能不依赖于PPAR-gamma激活，需要进一步阐明。(C)2001 Elsevier Science Inc. All rights reserved.
Apoptosis at the site of rupture has been proposed to play a role in premature rupture of the fetal membranes, a condition associated with increased risk of neonatal sepsis and preterm birth. We investigated the ability of peroxisome proliferator-activated receptor (PPAR)-gamma ligands 15-deoxy-Delta(12,14)PGJ(2) (15d-PGJ(2)), Delta(12)PGJ2(,) ciglitizone and rosiglitazone to induce apoptosis in the amnion-like WISH cell line. 15d-PGJ(2) (10 muM) induced morphological characteristics of apoptosis within 2 h, with biochemical indices (caspase activation and substrate cleavage) following shortly after; maximum cell death (approximately 60%) was observed by 16 h, with an EC50 of approximately 7 muM 15d-PGJ(2). Delta(12)-PGJ(2) also induced apoptosis but was less potent and acted at a much slower rate. While ciglitizone also induced apoptosis, rosiglitazone had no effect on cell viability. The mechanism of induction of apoptosis by 15d-PGJ(2) and Delta(12)PGJ(2), which may be independent of PPAR-gamma activation, requires further elucidation. (C) 2001 Elsevier Science Inc. All rights reserved.