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Neurotoxic and neuroprotective actions of catecholamines in cortical neurons.

Authors
Noh, JS; Kim, EY; Kang, JS; Kim, HR; Oh, YJ; Gwag, BJ
Citation
Experimental neurology, 159(1):217-224, 1999
Journal Title
Experimental neurology
ISSN
0014-48861090-2430
Abstract
We examined the possibility that catecholamines (CA) could act as endogenous modulators of neuronal death. Exposure to high doses (>100 microM) of dopamine (DA) caused widespread neuronal death within 24 h in mouse cortical cell cultures and was accompanied by cell body shrinkage, aggregation and condensation of nuclear chromatin, and prominent internucleosomal DNA fragmentation. Epinephrine, but not norepinephrine (NE), was slightly toxic to neurons at doses higher than 1 mM. DA-induced death was attenuated by the addition of three different anti-apoptosis agents, 1 microgram/ml cycloheximide, 25 mM K(+), or 100 ng/ml brain-derived neurotrophic factor (BDNF). While treatment with 100 microM N-acetyl-l-cysteine attenuated DA neurotoxicity, neither the glutamate antagonists (10 microM MK-801 plus 50 microM CNQX) nor several antioxidants [trolox, 100 microM; Mn (III) tetrakis (4-benzoic acid) porphyrin chloride, 100 microM; Mn (III) tetrakis (1-methyl-4-pyridyl) prophyrin pentachloride, 100 microM; N-tert-butyl-alpha-phenylnitrone, 3 mM] prevented the CA-induced apoptosis. Interestingly, all CA at 1-30 microM attenuated free radical-mediated neuronal necrosis following exposure to 30 microM Fe(2+) or 200 microM H(2)O(2), which was insensitive to DA or NE antagonists. Like trolox, CA reduced levels of the stable free radical 1,1-diphenyl-2-picrylhydrazyl under cell-free conditions, raising the possibility that CA as an antioxidant protects neurons. We also found that the neuroprotective effect of CA prolonged the protective effects of BDNF against serum deprivation. The present findings suggest that CA induces apoptosis at high doses but prevents free radical-mediated neurotoxicity as an anti-oxidant without being coupled to the receptors.
MeSH terms
Acetylcysteine/metabolismAnimalsApoptosis/drug effects*Brain-Derived Neurotrophic Factor/pharmacologyCardiotonic Agents/toxicityCatecholamines/toxicity*Cell Survival/drug effectsCells, CulturedCerebral Cortex/cytologyCycloheximide/pharmacologyDNA DamageDopamine/toxicityDose-Response Relationship, DrugDrug InteractionsEpinephrine/toxicityFetus/cytologyFree Radicals/metabolismLipid PeroxidationMiceNeurons/cytology*Neurons/drug effectsNeurons/metabolismNorepinephrine/toxicityPotassium/pharmacologyProtein Synthesis Inhibitors/pharmacologySympathomimetics/toxicity
DOI
10.1006/exnr.1999.7144
PMID
10486189
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Psychiatry & Behavioural Sciences
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
AJOU Authors
노, 재성곽, 병주
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