PMID- 16702990
OWN - NLM
STAT- MEDLINE
DCOM- 20061226
LR  - 20181201
IS  - 0007-1188 (Print)
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Linking)
VI  - 148
IP  - 5
DP  - 2006 Jul
TI  - Moclobemide upregulated Bcl-2 expression and induced neural stem cell 
      differentiation into serotoninergic neuron via extracellular-regulated kinase 
      pathway.
PG  - 587-98
AB  - 1. Moclobemide (MB) is an antidepressant drug that selectively and reversibly 
      inhibits monoamine oxidase-A. Recent studies have revealed that antidepressant 
      drugs possess the characters of potent growth-promoting factors for the 
      development of neurogenesis and improve the survival rate of serotonin 
      (5-hydroxytrytamine; 5-HT) neurons. However, whether MB comprises neuroprotection 
      effects or modulates the proliferation of neural stem cells (NSCs) needs to be 
      elucidated. 2. In this study, firstly, we used the MTT 
      (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay to 
      demonstrate that 50 microM MB can increase the cell viability of NSCs. The result 
      of real-time reverse transcription-polymerase chain reaction (RT-PCR) showed that 
      the induction of MB can upregulate the gene expressions of Bcl-2 and Bcl-xL. By 
      using caspases 8 and 3, ELISA and terminal dUTP nick-end labeling (TUNEL) assay, 
      our data further confirmed that 50 microM MB-treated NSCs can prevent 
      FasL-induced apoptosis. 3. The morphological findings also supported the evidence 
      that MB can facilitate the dendritic development and increase the neurite 
      expansion of NSCs. Moreover, we found that MB treatment increased the expression 
      of Bcl-2 in NSCs through activating the extracellular-regulated kinase (ERK) 
      phosphorylation. 4. By using the triple-staining immunofluorescent study, the 
      percentages of serotonin- and MAP-2-positive cells in the day 7 culture of 
      MB-treated NSCs were significantly increased (P<0.01). Furthermore, our data 
      supported that MB treatment increased functional production of serotonin in NSCs 
      via the modulation of ERK1/2. In sum, the study results support that MB can 
      upregulate Bcl-2 expression and induce the differentiation of NSCs into 
      serotoninergic neuron via ERK pathway.
FAU - Chiou, Shih-Hwa
AU  - Chiou SH
AD  - Department of Medical Research and Education, Taipei Veterans General Hospital 
      and National Yang-Ming University, Taipei, Taiwan. shchiou@vghtpe.gov.tw
FAU - Ku, Hung-Hai
AU  - Ku HH
FAU - Tsai, Tung-Hu
AU  - Tsai TH
FAU - Lin, Heng-Liang
AU  - Lin HL
FAU - Chen, Li-Hsin
AU  - Chen LH
FAU - Chien, Chan-Shiu
AU  - Chien CS
FAU - Ho, Larry L-T
AU  - Ho LL
FAU - Lee, Chen-Hsen
AU  - Lee CH
FAU - Chang, Yuh-Lih
AU  - Chang YL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060515
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 333DO1RDJY (Serotonin)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - PJ0Y7AZB63 (Moclobemide)
SB  - IM
CIN - Br J Pharmacol. 2006 Jul;148(5):563-4. PMID: 16702988
MH  - Animals
MH  - Apoptosis Regulatory Proteins/analysis/metabolism
MH  - Cell Differentiation/*drug effects
MH  - Cell Survival/drug effects
MH  - Chromatography, High Pressure Liquid
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism/*physiology
MH  - Gene Expression Regulation/drug effects
MH  - In Situ Nick-End Labeling
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - Moclobemide/*pharmacology
MH  - Neurites/drug effects
MH  - Neurons/*drug effects/metabolism
MH  - Phosphorylation/drug effects
MH  - Proto-Oncogene Proteins c-bcl-2/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Serotonin/*metabolism
MH  - Signal Transduction
MH  - Stem Cells/*drug effects
PMC - PMC1751873
EDAT- 2006/05/17 09:00
MHDA- 2006/12/27 09:00
PMCR- 2007/07/01
CRDT- 2006/05/17 09:00
PHST- 2006/05/17 09:00 [pubmed]
PHST- 2006/12/27 09:00 [medline]
PHST- 2006/05/17 09:00 [entrez]
PHST- 2007/07/01 00:00 [pmc-release]
AID - 0706766 [pii]
AID - 10.1038/sj.bjp.0706766 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2006 Jul;148(5):587-98. doi: 10.1038/sj.bjp.0706766. Epub 2006 
      May 15.