15-deoxy-delta12,14-prostaglandin J2-induced apoptosis in amnion-like WISH cells

J Keelan; R Helliwell; B Nijmeijer; E Berry; T Sato; K Marvin; M Mitchell; R Gilmour

doi:10.1016/s0090-6980(01)00164-2

15-deoxy-delta12,14-prostaglandin J2-induced apoptosis in amnion-like WISH cells

Prostaglandins Other Lipid Mediat. 2001 Dec;66(4):265-82. doi: 10.1016/s0090-6980(01)00164-2.

Authors

J Keelan¹, R Helliwell, B Nijmeijer, E Berry, T Sato, K Marvin, M Mitchell, R Gilmour

Affiliation

¹ Liggins Institute and Divisions of Pharmacology, University of Auckland Faculty of Medical and Health Sciences, New Zealand. j.keelan@auckland.ac.nz

PMID: 11785780
DOI: 10.1016/s0090-6980(01)00164-2

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Chloromethyl Ketones / pharmacology
Amnion / drug effects*
Amnion / pathology
Apoptosis / drug effects
Caspase Inhibitors
Caspases / drug effects
Caspases / metabolism
Cell Survival / drug effects
Cells, Cultured
Cysteine Proteinase Inhibitors / pharmacology
Enzyme Activation / drug effects
Humans
Hypoglycemic Agents / pharmacology
Immunologic Factors / pharmacology
Ligands
Prostaglandin D2 / analogs & derivatives*
Prostaglandin D2 / pharmacology*
Receptors, Cytoplasmic and Nuclear / metabolism
Rosiglitazone
Thiazoles / pharmacology
Thiazolidinediones*
Time Factors
Transcription Factors / metabolism

Substances

15-deoxy-delta(12,14)-prostaglandin J2
Amino Acid Chloromethyl Ketones
Caspase Inhibitors
Cysteine Proteinase Inhibitors
Hypoglycemic Agents
Immunologic Factors
Ligands
Receptors, Cytoplasmic and Nuclear
Thiazoles
Thiazolidinediones
Transcription Factors
benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
Rosiglitazone
Caspases
Prostaglandin D2
ciglitazone