PMID- 10486189
OWN - NLM
STAT- MEDLINE
DCOM- 19991007
LR  - 20220311
IS  - 0014-4886 (Print)
IS  - 0014-4886 (Linking)
VI  - 159
IP  - 1
DP  - 1999 Sep
TI  - Neurotoxic and neuroprotective actions of catecholamines in cortical neurons.
PG  - 217-24
AB  - 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.
CI  - Copyright 1999 Academic Press.
FAU - Noh, J S
AU  - Noh JS
AD  - Department of Psychiatry and Behavioral Sciences, Ajou University, School of 
      Medicine, Suwon, Kyungkido, 442-749, Korea.
FAU - Kim, E Y
AU  - Kim EY
FAU - Kang, J S
AU  - Kang JS
FAU - Kim, H R
AU  - Kim HR
FAU - Oh, Y J
AU  - Oh YJ
FAU - Gwag, B J
AU  - Gwag BJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cardiotonic Agents)
RN  - 0 (Catecholamines)
RN  - 0 (Free Radicals)
RN  - 0 (Protein Synthesis Inhibitors)
RN  - 0 (Sympathomimetics)
RN  - 98600C0908 (Cycloheximide)
RN  - RWP5GA015D (Potassium)
RN  - VTD58H1Z2X (Dopamine)
RN  - WYQ7N0BPYC (Acetylcysteine)
RN  - X4W3ENH1CV (Norepinephrine)
RN  - YKH834O4BH (Epinephrine)
SB  - IM
MH  - Acetylcysteine/metabolism
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Brain-Derived Neurotrophic Factor/pharmacology
MH  - Cardiotonic Agents/toxicity
MH  - Catecholamines/*toxicity
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology
MH  - Cycloheximide/pharmacology
MH  - DNA Damage
MH  - Dopamine/toxicity
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Epinephrine/toxicity
MH  - Fetus/cytology
MH  - Free Radicals/metabolism
MH  - Lipid Peroxidation
MH  - Mice
MH  - Neurons/*cytology/drug effects/metabolism
MH  - Norepinephrine/toxicity
MH  - Potassium/pharmacology
MH  - Protein Synthesis Inhibitors/pharmacology
MH  - Sympathomimetics/toxicity
EDAT- 1999/09/16 00:00
MHDA- 1999/09/16 00:01
CRDT- 1999/09/16 00:00
PHST- 1999/09/16 00:00 [pubmed]
PHST- 1999/09/16 00:01 [medline]
PHST- 1999/09/16 00:00 [entrez]
AID - S0014-4886(99)97144-3 [pii]
AID - 10.1006/exnr.1999.7144 [doi]
PST - ppublish
SO  - Exp Neurol. 1999 Sep;159(1):217-24. doi: 10.1006/exnr.1999.7144.