Prostaglandin E2 induces apoptosis in cultured rat microglia

Autor: Shinya H. Kimura, Motohiko Takemura, Takayuki Nagano
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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