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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-4-12
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1872-7972
pubmed:author
pubmed:copyrightInfo
Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
26
pubmed:volume
474
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
109-14
pubmed:meshHeading
pubmed-meshheading:20298757-Analysis of Variance, pubmed-meshheading:20298757-Animals, pubmed-meshheading:20298757-Apoptosis, pubmed-meshheading:20298757-Brain, pubmed-meshheading:20298757-Butadienes, pubmed-meshheading:20298757-Caspase 3, pubmed-meshheading:20298757-Disease Models, Animal, pubmed-meshheading:20298757-Doxycycline, pubmed-meshheading:20298757-Enzyme Inhibitors, pubmed-meshheading:20298757-Gene Expression Regulation, Enzymologic, pubmed-meshheading:20298757-In Situ Nick-End Labeling, pubmed-meshheading:20298757-Infarction, Middle Cerebral Artery, pubmed-meshheading:20298757-Male, pubmed-meshheading:20298757-Matrix Metalloproteinase 9, pubmed-meshheading:20298757-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:20298757-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:20298757-Nitriles, pubmed-meshheading:20298757-Physical Conditioning, Animal, pubmed-meshheading:20298757-Rats, pubmed-meshheading:20298757-Rats, Sprague-Dawley, pubmed-meshheading:20298757-Reperfusion, pubmed-meshheading:20298757-Time Factors
pubmed:year
2010
pubmed:articleTitle
Matrix metalloproteinase-9 (MMP-9) expression and extracellular signal-regulated kinase 1 and 2 (ERK1/2) activation in exercise-reduced neuronal apoptosis after stroke.
pubmed:affiliation
Department of Neurological Surgery, Wayne State University School of Medicine, Detroit, MI 48201, United States.
pubmed:publicationType
Journal Article