Document Detail

Matrix metalloproteinase-9 (MMP-9) expression and extracellular signal-regulated kinase 1 and 2 (ERK1/2) activation in exercise-reduced neuronal apoptosis after stroke.
MedLine Citation:
PMID:  20298757     Owner:  NLM     Status:  MEDLINE    
Exercise preconditioning has been shown to reduce neuronal damage in ischemic/reperfusion (I/R) injury. ERK1/2 signaling in injury has been thought to modulate neuroprotection. In this study, we investigated the effects of ERK1/2 activation on the expression and activity of MMP-9 and downstream neuronal apoptosis. Adult male Sprague-Dawley rats were subjected to 30min of exercise on a treadmill for 3 weeks. Stroke was induced by a 2-h middle cerebral artery (MCA) occlusion using an intraluminal filament. Apoptotic protein caspase-3 and neuronal apoptosis in cortex and striatum was determined by Western blot at 24h reperfusion and TUNEL staining at 48h reperfusion in 5 I/R injury groups: no treatment, MMP-9 inhibitor (doxycycline), pre-ischemic exercise, exercised animals undergone ERK1/2 inhibition (U0126), and dual inhibition of ERK1/2 and MMP-9 in exercised ischemic rats. Cerebral MMP-9 expression in ischemic rats with different treatment was determined at 6, 12 and 24h reperfusion by real-time PCR for mRNA, Western blot for protein and zymography for enzyme activity. Exercise preconditioning significantly (p<0.05) reduced apoptosis determined by caspase-3 and TUNEL. In non-exercised rats, doxycycline treatment had significant (p<0.05) reductions in apoptosis after I/R injury. The dual ERK1/2-MMP-9 inhibited exercised animals had significantly (p<0.05) reduced neuronal apoptosis that was similar to that seen in exercised ischemic rats. MMP-9 expression in I/R injury was significantly (p<0.05) reduced in the exercised animals as compared to non-exercised controls. When ERK1/2 was inhibited, the reduced MMP-9 expression was reversed to the level seen in the non-exercised controls. This study has suggested that exercise-induced neuroprotection in I/R injury may be mediated by MMP-9 and ERK1/2 expression, leading to a reduction in neuronal apoptosis.
Khawar Chaudhry; Ryan Rogers; Miao Guo; Qin Lai; Gunjan Goel; Brandon Liebelt; Xunming Ji; Alecia Curry; Aaron Carranza; David F Jimenez; Yuchuan Ding
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Publication Detail:
Type:  Journal Article     Date:  2010-03-16
Journal Detail:
Title:  Neuroscience letters     Volume:  474     ISSN:  1872-7972     ISO Abbreviation:  Neurosci. Lett.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-04-12     Completed Date:  2010-07-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600130     Medline TA:  Neurosci Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  109-14     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
Department of Neurological Surgery, Wayne State University School of Medicine, Detroit, MI 48201, United States.
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MeSH Terms
Analysis of Variance
Apoptosis / drug effects,  physiology*
Brain / drug effects,  enzymology,  pathology
Butadienes / pharmacology
Caspase 3 / metabolism
Disease Models, Animal
Doxycycline / pharmacology
Enzyme Inhibitors / pharmacology
Gene Expression Regulation, Enzymologic / drug effects,  physiology
In Situ Nick-End Labeling / methods
Infarction, Middle Cerebral Artery / drug therapy,  pathology,  physiopathology,  rehabilitation*
Matrix Metalloproteinase 9 / metabolism*
Mitogen-Activated Protein Kinase 1 / metabolism*
Mitogen-Activated Protein Kinase 3 / metabolism*
Nitriles / pharmacology
Physical Conditioning, Animal / methods*
Rats, Sprague-Dawley
Reperfusion / methods
Time Factors
Reg. No./Substance:
0/Butadienes; 0/Enzyme Inhibitors; 0/Nitriles; 0/U 0126; 564-25-0/Doxycycline; EC Protein Kinase 1; EC Protein Kinase 3; EC 3.4.22.-/Caspase 3; EC Metalloproteinase 9

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