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Neuroprotective effects of prostaglandin E 2 or cAMP against microglial and neuronal free radical mediated toxicity associated with inflammation
Author(s) -
Kim Eun Joo,
Kwon Kyoung Ja,
Park JeeYoung,
Lee Soo Hwan,
Moon ChangHyun,
Baik Eun Joo
Publication year - 2002
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10373
Subject(s) - neuroprotection , neurotoxicity , prostaglandin e , nitric oxide , proinflammatory cytokine , forskolin , nitric oxide synthase , programmed cell death , reactive oxygen species , chemistry , apoptosis , pharmacology , prostaglandin e2 , tunel assay , biology , inflammation , biochemistry , toxicity , endocrinology , immunology , receptor , organic chemistry
Prostaglandin E 2 (PGE 2 ), a product of the cyclooxygenation of arachidonic acid released from membrane phospholipids, plays a critical role in inflammatory neurodegenerative conditions. Despite its classic role as a proinflammatory molecule, exogenous PGE 2 was suggested to have protective roles against neuronal death, although the exact protective mechanisms of PGE 2 are not yet defined. Thus, the aim of this study was to examine the effect of exogenous PGE 2 on inflammatory neurotoxicity. Lipopolysaccharide (LPS) induced neuronal toxicity, which was associated with terminal transferase dUTP nick end labeling (TUNEL)‐positive neuronal death with increased caspase‐3 activity. In neuron‐glial coculture, LPS markedly induced inducible nitric oxide synthase/nitric oxide (iNOS/NO) release from microglial cells, but not from neurons; however, LPS‐induced oxidative stress such as reactive oxygen species (ROS), measured with 2,7‐dichlorofluorescein diacetate oxidation, was increased in neurons, but not in microglial cells. Exogenous PGE 2 (1 μg/ml) rescued the neurons, reducing iNOS/NO release from microglial cells and ROS formation from neurons. PGE 2 has been known to increase intracelluar cyclic adenosine monophosphate (cAMP) levels. In this study, we found that intracellular cAMP elevating agents, forskolin, and cAMP analogue, dbcAMP and 8‐Br‐cAMP, also prevented LPS‐induced neuronal death. Thus, these results indicate that exogenous PGE 2 protects against LPS‐induced neuronal apoptotic cell death through the intracellular cAMP system, and is associated with the modulation of NO from microglial cells and ROS production from neurons. © 2002 Wiley‐Liss, Inc.