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Neuroprotective effects of prostaglandin E2 or cAMP against microglial and neuronal free radical mediated toxicity associated with inflammation.

Kim, EJ; Kwon, KJ; Park, JY; Lee, SH; Moon, CH; Baik, EJ
Journal of neuroscience research, 70(1):97-107, 2002
Journal Title
Journal of neuroscience research
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 microg/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.
MeSH terms
ActinsAnalysis of VarianceAnimalsApoptosis/*drug effectsBlotting, NorthernBlotting, WesternBrainCaspase 3Caspases/metabolismCell Death/drug effectsCells, CulturedCyclic AMP/*pharmacologyDinoprostone/*pharmacologyDrug Interactions/physiologyFetusFluoresceins/chemistryForskolinFree Radicals/metabolismImmunohistochemistryIn Situ Nick-End LabelingLipopolysaccharides/toxicityMiceMice, Inbred ICRMicroglia/cytology/*drug effects/metabolismNeurons/cytology/*drug effects/metabolismNeuroprotective Agents/pharmacologyNitric Oxide/metabolismNitric Oxide Synthase/metabolismNitric Oxide Synthase Type IINitrites/metabolismRNA, MessengerReactive Oxygen Species/metabolismReverse Transcriptase Polymerase Chain Reaction
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
AJOU Authors
이, 수환문, 창현백, 은주
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