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The neuroprotective role of tissue inhibitor of metalloproteinase-2 in MPP+- or 6-OHDA-treated SK-N-BE(2)C and SH-SY5Y human neuroblastoma cells

Title
The neuroprotective role of tissue inhibitor of metalloproteinase-2 in MPP+- or 6-OHDA-treated SK-N-BE(2)C and SH-SY5Y human neuroblastoma cells
Authors
Kim S.-Y.Woo M.-S.Park J.-S.Hyun J.-W.Kim Y.-S.Kim H.-S.
Ewha Authors
김희선박진선
SCOPUS Author ID
김희선scopus; 박진선scopus
Issue Date
2010
Journal Title
Neuroscience Letters
ISSN
0304-3940JCR Link
Citation
vol. 468, no. 2, pp. 136 - 140
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors of matrix metalloproteinases (MMPs), and the aberrant expressions of MMPs are strongly associated with neuroinflammation and neuronal cell death. In the present study, we found that two well-known dopaminergic neurotoxins, MPP+ and 6-OHDA, reduced TIMP-2 expression at the mRNA and protein levels in two human neuroblastoma cell lines (SK-N-BE(2)C and SH-SY5Y). To investigate the role of TIMP-2, these cells were transfected with TIMP-2 expression plasmid and viabilities were compared after treating cells with MPP+ or 6-OHDA. It was found that TIMP-2 overexpression attenuated the cell deaths induced by MPP+ or 6-OHDA, and that the degree of protection conferred was greater for MPP+-treated cells. Furthermore, the introduction of TIMP-2 siRNA into SK-N-BE(2)C cells aggravated the cell deaths induced by MPP+ or 6-OHDA. These findings collectively show that endogenously expressed TIMP-2 has a neuroprotective role, and they imply that the inhibition of TIMP-2 expression by MPP+ or 6-OHDA may contribute, in part, to neuronal cell death. These findings suggest that TIMP-2 expressional enhancement provides a potential therapeutic strategy for the treatment of neurodegenerative diseases such as Parkinson's disease. © 2009 Elsevier Ireland Ltd. All rights reserved.
DOI
10.1016/j.neulet.2009.10.084
Appears in Collections:
의학전문대학원 > 의학과 > Journal papers
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