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15-deoxy-delta12,14-prostaglandin J2-induced apoptosis in amnion-like WISH cells
J Keelan1, R Helliwell, B Nijmeijer
1Liggins Institute and Divisions of Pharmacology, University of Auckland Faculty of Medical and Health Sciences, New Zealand. j.keelan@auckland.ac.nz
Insights
Certain PPAR-gamma ligands, like 15d-PGJ2, induce apoptosis in fetal membrane cells, potentially impacting preterm birth and neonatal sepsis risk. Further research is needed to understand the exact mechanism.
Area of Science:
- Cell Biology
- Obstetrics
- Biochemistry
Background:
- Premature rupture of fetal membranes is linked to neonatal sepsis and preterm birth.
- Apoptosis at the rupture site is a proposed contributing factor.
Purpose of the Study:
- To investigate the apoptotic effects of peroxisome proliferator-activated receptor (PPAR)-gamma ligands on amnion cells.
- To assess the potency and kinetics of different PPAR-gamma ligands in inducing apoptosis.
Main Methods:
- WISH cell line used to model amnion cells.
- Treatment with PPAR-gamma ligands: 15-deoxy-delta12,14PGJ2 (15d-PGJ2), delta12PGJ2, ciglitizone, and rosiglitazone.
- Morphological and biochemical assessment of apoptosis, including caspase activation and cell viability assays.
Main Results:
- 15d-PGJ2 induced significant apoptosis (approx. 60% cell death) with an EC50 of ~7 microM.
- Delta12-PGJ2 also induced apoptosis, but was less potent and slower acting.
- Ciglitizone showed some apoptotic effect, while rosiglitazone had no impact on cell viability.
Conclusions:
- 15d-PGJ2 is a potent inducer of apoptosis in amnion-like cells.
- The mechanism of apoptosis induction by 15d-PGJ2 and delta12PGJ2 may not solely depend on PPAR-gamma activation.
- Further studies are required to fully elucidate the apoptotic pathways involved.
Abstract:
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-delta12,14PGJ2 (15d-PGJ2), delta12PGJ2, ciglitizone and rosiglitazone to induce apoptosis in the amnion-like WISH cell line. 15d-PGJ2 (10 microM) 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 microM 15d-PGJ2. Delta12-PGJ2 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-PGJ2 and delta12PGJ2, which may be independent of PPAR-gamma activation, requires further elucidation.