Matrix metalloproteinase-9 (MMP-9) expression and extracellular signal-regulated kinase 1 and 2 (ERK1/2) activation in exercise-reduced neuronal apoptosis after stroke

Khawar Chaudhry, Ryan Rogers, Miao Guo, Qin Lai, Gunjan Goel, Brandon Liebelt, Xunming Ji, Alecia Curry, Aaron Carranza, David F. Jimenez, Yuchuan Ding

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

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 30. min 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 24. h reperfusion and TUNEL staining at 48. h 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 24. h 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.

Original languageEnglish (US)
Pages (from-to)109-114
Number of pages6
JournalNeuroscience Letters
Volume474
Issue number2
DOIs
StatePublished - Apr 1 2010

Keywords

  • Ischemia/reperfusion
  • Preconditioning
  • TUNEL staining

ASJC Scopus subject areas

  • Neuroscience(all)

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    Chaudhry, K., Rogers, R., Guo, M., Lai, Q., Goel, G., Liebelt, B., Ji, X., Curry, A., Carranza, A., Jimenez, D. F., & Ding, Y. (2010). Matrix metalloproteinase-9 (MMP-9) expression and extracellular signal-regulated kinase 1 and 2 (ERK1/2) activation in exercise-reduced neuronal apoptosis after stroke. Neuroscience Letters, 474(2), 109-114. https://doi.org/10.1016/j.neulet.2010.03.020