Prostaglandin E(2) induces caspase-dependent apoptosis in rat cortical cells.

Abstract:

:Up-regulation of neuronal cyclooxygenase-2 (COX-2) and the elevation in prostaglandin E(2) (PGE(2)) have been reported to occur after cerebral ischemic insult. To evaluate whether the COX-2 reaction product PGE(2) is directly related to induction of apoptosis in neuronal cells, the effect of PGE(2) on cell viability was examined in rat cortical cells. PGE(2) induced apoptosis in a dose-dependent manner (5-25 microM) 48 h after addition to the cells, which was characterized by cell shrinkage, nuclear condensation or fragmentation, and internucleosomal DNA fragmentation. Neither 17-phenyl trinor-prostaglandin E(2) (an EP1 agonist) or sulprostone (an EP3 agonist) induced cell death, whereas butaprost (an EP2 agonist) induced apoptotic cell death. In addition, PGE(2) activated caspase-3 in a time-dependent manner until 24 h after treatment. The apoptosis induced by PGE(2) was prevented by a caspase-3 inhibitor in a dose-dependent manner. In contrast, dibutyryl cyclic adenosine monophosphate also induced apoptotic cell death in a dose-dependent manner (20-100 microM). These results suggest that PGE(2), acting via an EP2-like receptor, induces apoptosis in neurons.

journal_name

Neurosci Lett

journal_title

Neuroscience letters

authors

Takadera T,Yumoto H,Tozuka Y,Ohyashiki T

doi

10.1016/s0304-3940(01)02449-1

keywords:

subject

Has Abstract

pub_date

2002-01-11 00:00:00

pages

61-4

issue

2

eissn

0304-3940

issn

1872-7972

pii

S0304394001024491

journal_volume

317

pub_type

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