PMID- 12123853
OWN - NLM
STAT- MEDLINE
DCOM- 20021028
LR  - 20220321
IS  - 0304-3940 (Print)
IS  - 0304-3940 (Linking)
VI  - 328
IP  - 1
DP  - 2002 Aug 2
TI  - Allopregnanolone attenuates N-methyl-D-aspartate-induced excitotoxicity and 
      apoptosis in the human NT2 cell line in culture.
PG  - 33-6
AB  - Progesterone modulates gamma-aminobutyric acid and excitatory amino acid 
      neurotransmitter systems and has neuroprotective properties in models of 
      hypoxia-ischemia. This study examined the in vitro effects of allopregnanolone, 
      the active progesterone metabolite, in models of N-methyl-D-aspartate 
      (NMDA)-induced necrosis and apoptosis. Cultured NT2 neurons were exposed to 1 mM 
      NMDA. Lactate dehydrogenase (LDH) release was measured 24 h later. NMDA at a 
      concentration of 1 mM produced a 39 +/- 19% release of total LDH. Exposure to 10 
      microM allopregnanolone prior to NMDA exposure reduced LDH release by 51% (P = 
      0.0028). NMDA stimulated apoptotic cell changes defined by terminal dUTP nick-end 
      labeling (TUNEL) and 5,5', 6,6'-tetrachloro-1,1,3,3'-tetra 
      ethlybenzimidazolycarbocyanide iodide staining were reduced to baseline values by 
      both 10 microM allopregnanolone and 100 microM MK-801. Pretreatment with 
      allopregnanolone (0-10 microM) reduced the percentage of TUNEL-positive cells in 
      a dose-dependent manner (EC(50) = 2.7 +/- 0.1 nM). Physiologic concentrations of 
      allopregnanolone provided protection against both necrotic and apoptotic injury 
      induced by NMDA excitotoxicity.
FAU - Lockhart, Ellen M
AU  - Lockhart EM
AD  - Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, 
      USA. ellen.lockhart@mcmail.vanderbilt.edu
FAU - Warner, David S
AU  - Warner DS
FAU - Pearlstein, Robert D
AU  - Pearlstein RD
FAU - Penning, Donald H
AU  - Penning DH
FAU - Mehrabani, Saeed
AU  - Mehrabani S
FAU - Boustany, Rose-Mary
AU  - Boustany RM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (Benzimidazoles)
RN  - 0 (Carbocyanines)
RN  - 0 (Excitatory Amino Acid Agonists)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Fluorescent Dyes)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Neurotoxins)
RN  - 21527-78-6 (5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - BXO86P3XXW (Pregnanolone)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
SB  - IM
MH  - Apoptosis/drug effects/*physiology
MH  - Asphyxia Neonatorum/*metabolism/physiopathology
MH  - Benzimidazoles
MH  - Carbocyanines
MH  - Cell Count
MH  - Cell Survival/drug effects/*physiology
MH  - Dizocilpine Maleate/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Excitatory Amino Acid Agonists/pharmacology
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Female
MH  - Fluorescent Dyes
MH  - Humans
MH  - Hypoxia-Ischemia, Brain/drug therapy/*metabolism/physiopathology
MH  - In Situ Nick-End Labeling
MH  - Infant, Newborn
MH  - L-Lactate Dehydrogenase/drug effects/metabolism
MH  - Membrane Potentials/drug effects
MH  - Mitochondria/drug effects/metabolism
MH  - N-Methylaspartate/pharmacology
MH  - Neurons/drug effects/*metabolism
MH  - Neuroprotective Agents/metabolism/*therapeutic use
MH  - Neurotoxins/pharmacology
MH  - Pregnancy
MH  - Pregnanolone/pharmacology/therapeutic use
MH  - Progesterone/metabolism/*therapeutic use
MH  - Tumor Cells, Cultured
EDAT- 2002/07/19 10:00
MHDA- 2002/10/29 04:00
CRDT- 2002/07/19 10:00
PHST- 2002/07/19 10:00 [pubmed]
PHST- 2002/10/29 04:00 [medline]
PHST- 2002/07/19 10:00 [entrez]
AID - S0304394002004482 [pii]
AID - 10.1016/s0304-3940(02)00448-2 [doi]
PST - ppublish
SO  - Neurosci Lett. 2002 Aug 2;328(1):33-6. doi: 10.1016/s0304-3940(02)00448-2.