Prostaglandin E2 induces apoptosis in cultured rat microglia
Autor: | Shinya H. Kimura, Motohiko Takemura, Takayuki Nagano |
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Rok vydání: | 2014 |
Předmět: |
Agonist
medicine.medical_specialty Programmed cell death Cell Survival medicine.drug_class Prostaglandin E2 receptor medicine.medical_treatment Blotting Western Apoptosis DNA Fragmentation Biology Dinoprostone chemistry.chemical_compound Internal medicine Cyclic AMP medicine Animals Cyclic adenosine monophosphate Alprostadil Rats Wistar Prostaglandin E2 Molecular Biology Cells Cultured L-Lactate Dehydrogenase PROSTAGLANDIN TRANSPORTER General Neuroscience Receptors Prostaglandin E EP2 Subtype Receptors Prostaglandin E EP1 Subtype Molecular biology Endocrinology chemistry Receptors Prostaglandin E EP3 Subtype lipids (amino acids peptides and proteins) Microglia Neurology (clinical) Poly(ADP-ribose) Polymerases Receptors Prostaglandin E EP4 Subtype Intracellular Developmental Biology Prostaglandin E medicine.drug |
Zdroj: | Brain Research. 1568:1-9 |
ISSN: | 0006-8993 |
Popis: | Prostaglandin E2 (PGE2) plays a critical role in the modulation of microglial function including migration and phagocytosis through EP2, which increases intracellular cyclic adenosine monophosphate (AMP) concentration. In the present study, we found that PGE2 reduces cell viability in microglia. PGE2 decreased 3-(4,5-dimethylthiazol-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) reduction and increased lactate dehydrogenase release, deoxyribonucleic acid fragmentation, and poly(ADP-ribose) polymerase cleavage after 24h incubation, suggesting that PGE2 induces apoptosis in these cells. An EP2 agonist, butaprost, and an EP4 agonist, PGE1 alcohol, also induced apoptosis, while an EP1 agonist, 17-phenyl trinor PGE2, or an EP3 agonist, sulprostone, at 10(-6)M did not. On the other hand, EP1-EP4 antagonists, SC-51322, AH6809, L-798106, or GW627368X, up to 10(-5)M did not affect the decrease in MTT reduction by PGE2. Intracellular cyclic AMP accumulation was induced by butaprost, but not 17-phenyl trinor PGE2, sulprostone, or PGE1 alcohol at 10(-6)M. Additionally, we previously reported that PGE2-induced intracellular cyclic AMP accumulation was reversed by AH6809. Besides EP receptors, one of other targets was thought to be prostaglandin transporter, but its inhibitors, bromocresol green or U-46619 up to 10(-5)M did not affect the decrease in MTT reduction by PGE2. These results suggest that PGE2 induces apoptosis in microglia independent of intracellular cyclic AMP concentration, and there are different mechanisms between PGE2-induced apoptosis and the modulation of microglial function. |
Databáze: | OpenAIRE |
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