PMID- 19815046
OWN - NLM
STAT- MEDLINE
DCOM- 20100504
LR  - 20131121
IS  - 1872-9754 (Electronic)
IS  - 0197-0186 (Linking)
VI  - 56
IP  - 1
DP  - 2010 Jan
TI  - Matrix metalloproteinase-3 contributes to vulnerability of the nigral 
      dopaminergic neurons.
PG  - 161-7
LID - 10.1016/j.neuint.2009.09.014 [doi]
AB  - Dopamine(DA)rgic neurons are particularly vulnerable due to the presence of 
      oxidative stress-inducing molecules such as DA, tetrahydrobiopterin, iron and 
      tyrosine hydroxylase (TH). We have recently observed that matrix 
      metalloproteinase-3 (MMP-3) is involved in degeneration of DArgic neurons. In the 
      present study, we sought to explore the role of MMP-3 in DArgic neurons not 
      exposed to apparent stress conditions. In 8-week-old male mice deficient of MMP-3 
      gene (MMP-3 KO), the total number of DArgic neurons in the substantia nigra was 
      considerably higher than wild type (WT). Primary cultured mesencephalic neurons 
      from MMP-3 KO showed higher [(3)H]DA uptake capability compared to that of WT. 
      The number of TH-immunopositive neurons and the length of average dendritic 
      branch were also greater. This appeared to be selective for the DArgic system, 
      because [(3)H]GABA uptake and calbindin D-28K and MAP-2 immunoreactivities were 
      unaltered. On the other hand, no differences were noted in the levels of the 
      striatal DA, DOPAC and BH4 and TH protein between the KO and WT. Interestingly, 
      TH immunodensity per cell was lower in the DArgic neurons of MMP-3 KO both in 
      primary culture and in vivo, suggesting the presence of a compensatory mechanism. 
      These results further indicate a role of MMP-3 in the demise of DArgic neurons 
      and suggest MMP-3 as a candidate cellular target for neuroprotective therapy.
CI  - 2009 Elsevier Ltd. All rights reserved.
FAU - Kim, Sung Tae
AU  - Kim ST
AD  - Department of Biochemistry and Molecular Biology, University of Ulsan College of 
      Medicine, Seoul, South Korea.
FAU - Kim, Eun-Mee
AU  - Kim EM
FAU - Choi, Ji Hyun
AU  - Choi JH
FAU - Son, Hyo Jin
AU  - Son HJ
FAU - Ji, In Jung
AU  - Ji IJ
FAU - Joh, Tong H
AU  - Joh TH
FAU - Chung, Sun Ju
AU  - Chung SJ
FAU - Hwang, Onyou
AU  - Hwang O
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091006
PL  - England
TA  - Neurochem Int
JT  - Neurochemistry international
JID - 8006959
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Cell Count
MH  - Cells, Cultured
MH  - Corpus Striatum/metabolism
MH  - Cytoprotection/drug effects/physiology
MH  - Dendrites/enzymology/pathology
MH  - Disease Models, Animal
MH  - Dopamine/*metabolism
MH  - Down-Regulation/genetics
MH  - Male
MH  - Matrix Metalloproteinase 3/*genetics
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Nerve Degeneration/*enzymology/pathology/physiopathology
MH  - Neurons/*enzymology/pathology
MH  - Parkinson Disease/enzymology/pathology/physiopathology
MH  - Substantia Nigra/*enzymology/pathology/physiopathology
MH  - Tyrosine 3-Monooxygenase/metabolism
MH  - gamma-Aminobutyric Acid/metabolism
EDAT- 2009/10/10 06:00
MHDA- 2010/05/05 06:00
CRDT- 2009/10/10 06:00
PHST- 2009/06/09 00:00 [received]
PHST- 2009/09/23 00:00 [revised]
PHST- 2009/09/24 00:00 [accepted]
PHST- 2009/10/10 06:00 [entrez]
PHST- 2009/10/10 06:00 [pubmed]
PHST- 2010/05/05 06:00 [medline]
AID - S0197-0186(09)00278-2 [pii]
AID - 10.1016/j.neuint.2009.09.014 [doi]
PST - ppublish
SO  - Neurochem Int. 2010 Jan;56(1):161-7. doi: 10.1016/j.neuint.2009.09.014. Epub 2009 
      Oct 6.