PMID- 19526291
OWN - NLM
STAT- MEDLINE
DCOM- 20100122
LR  - 20211020
IS  - 1476-3524 (Electronic)
IS  - 1029-8428 (Print)
IS  - 1029-8428 (Linking)
VI  - 16
IP  - 2
DP  - 2009 Aug
TI  - Glyceraldehyde-3-phosphate dehydrogenase-monoamine oxidase B-mediated cell 
      death-induced by ethanol is prevented by rasagiline and 1-R-aminoindan.
PG  - 148-59
LID - 10.1007/s12640-009-9064-7 [doi]
AB  - The inhibitors of monoamine oxidase B (MAO B) are effectively used as therapeutic 
      drugs for neuropsychiatric and neurodegenerative diseases. However, their 
      mechanism of action is not clear, since the neuroprotective effect of MAO B 
      inhibitors is associated with the blockage of glyceraldehyde-3-phosphate 
      dehydrogenase (GAPDH)-death cascade, rather than the inhibition of MAO B. Here, 
      we provide evidence that GAPDH potentiates the ethanol-induced activity of MAO B 
      and brain cell toxicity. The levels of nuclear GAPDH and MAO B activity are 
      significantly increased in brain-derived cell lines upon 75 mM ethanol-induced 
      cell death. Over-expression of GAPDH in cells enhances ethanol-induced cell 
      death, and also increases the ethanol-induced activation of MAO B. In contrast, 
      the MAO B inhibitors rasagiline and selegiline (0.25 nM) and the rasagiline 
      metabolite, 1-R-aminoindan (1 muM) decreases the ethanol-induced MAO B, prevents 
      nuclear translocation of GAPDH and reduces cell death. In addition, GAPDH 
      interacts with transforming growth factor-beta-inducible early gene (TIEG2), a 
      transcriptional activator for MAO B, and this interaction is increased in the 
      nucleus by ethanol but reduced by MAO B inhibitors and 1-R-aminoindan. 
      Furthermore, silencing TIEG2 using RNAi significantly reduces GAPDH-induced MAO B 
      upregulation and neurotoxicity. In summary, ethanol-induced cell death, 
      attenuated by MAO B inhibitors, may result from disrupting the movement of GAPDH 
      with the transcriptional activator into the nucleus and secondly inhibit MAO B 
      gene expression. Thus, the neuroprotective effects of rasagiline or 
      1-R-aminoindan on ethanol-induced cell death mediated by a novel GAPDH-MAO B 
      pathway may provide a new insight in the treatment of neurobiological diseases 
      including alcohol-use disorders.
FAU - Ou, Xiao-Ming
AU  - Ou XM
AD  - Division of Neurobiology & Behavioral Research, Department of Psychiatry and 
      Human Behavior (G-109), University of Mississippi Medical Center, 2500 N. State 
      Street, Jackson, MS 39216, USA. xou@psychiatry.umsmed.edu
FAU - Lu, Deyin
AU  - Lu D
FAU - Johnson, Chandra
AU  - Johnson C
FAU - Chen, Kevin
AU  - Chen K
FAU - Youdim, Moussa B H
AU  - Youdim MB
FAU - Rajkowska, Grazyna
AU  - Rajkowska G
FAU - Shih, Jean C
AU  - Shih JC
LA  - eng
GR  - P20 RR17701/RR/NCRR NIH HHS/United States
GR  - P20 RR017701-086006/RR/NCRR NIH HHS/United States
GR  - R01 MH067968-05/MH/NIMH NIH HHS/United States
GR  - P20 RR017701/RR/NCRR NIH HHS/United States
GR  - R37 MH039085-23/MH/NIMH NIH HHS/United States
GR  - R37 MH39085/MH/NIMH NIH HHS/United States
GR  - R37 MH039085/MH/NIMH NIH HHS/United States
GR  - P20 RR017701-086001/RR/NCRR NIH HHS/United States
GR  - R01 MH67968/MH/NIMH NIH HHS/United States
GR  - P20 RR017701-086000/RR/NCRR NIH HHS/United States
GR  - R01 MH067968/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090528
PL  - United States
TA  - Neurotox Res
JT  - Neurotoxicity research
JID - 100929017
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Central Nervous System Depressants)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Indans)
RN  - 0 (KLF11 protein, human)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Repressor Proteins)
RN  - 0 (aminoindanol)
RN  - 003N66TS6T (rasagiline)
RN  - 3K9958V90M (Ethanol)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.2.1.- (Glyceraldehyde-3-Phosphate Dehydrogenases)
RN  - EC 1.4.3.4 (Monoamine Oxidase)
SB  - IM
MH  - Analysis of Variance
MH  - Apoptosis Regulatory Proteins
MH  - Cell Cycle Proteins/genetics
MH  - Cell Death/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Central Nervous System Depressants/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Enzyme Inhibitors/pharmacology
MH  - Ethanol/*pharmacology
MH  - Gene Expression Regulation, Enzymologic/drug effects
MH  - Glyceraldehyde-3-Phosphate Dehydrogenases/*metabolism
MH  - Humans
MH  - Hydrogen Peroxide/metabolism
MH  - Immunoprecipitation/methods
MH  - Indans/*pharmacology
MH  - Monoamine Oxidase/genetics/*metabolism
MH  - Neuroprotective Agents/*pharmacology
MH  - Protein Transport/drug effects
MH  - RNA, Small Interfering/pharmacology
MH  - Repressor Proteins/genetics
PMC - PMC2862453
MID - NIHMS195158
EDAT- 2009/06/16 09:00
MHDA- 2010/01/23 06:00
PMCR- 2010/05/03
CRDT- 2009/06/16 09:00
PHST- 2009/02/12 00:00 [received]
PHST- 2009/05/06 00:00 [accepted]
PHST- 2009/04/21 00:00 [revised]
PHST- 2009/06/16 09:00 [entrez]
PHST- 2009/06/16 09:00 [pubmed]
PHST- 2010/01/23 06:00 [medline]
PHST- 2010/05/03 00:00 [pmc-release]
AID - 10.1007/s12640-009-9064-7 [doi]
PST - ppublish
SO  - Neurotox Res. 2009 Aug;16(2):148-59. doi: 10.1007/s12640-009-9064-7. Epub 2009 
      May 28.