Exercise preconditioning reduces neuronal apoptosis in stroke by up-regulating heat shock protein-70 (heat shock protein-72) and extracellular-signal-regulated-kinase 1/2

B. Liebelt, P. Papapetrou, A. Ali, M. Guo, X. Ji, C. Peng, R. Rogers, A. Curry, D. Jimenez, Y. Ding

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

Exercise preconditioning induces neuroprotection after stroke. We investigated the beneficial role of heat shock protein-70 (HSP-70) and phosphorylated extracellular-signal-regulated-kinase 1/2 (pERK 1/2), as they pertain to reducing apoptosis and their influence on Bcl-xL, Bax, and apoptosis-inducing factor (AIF) in rats subjected to ischemia and reperfusion. Adult male Sprague-Dawley rats were subjected to 30 min of exercise on a treadmill for 1, 2, or 3 weeks. Stroke was induced by a 2-h middle cerebral artery (MCA) occlusion using an intraluminal filament. Protein levels of HSP-70, pERK 1/2, Bcl-xL, Bax, and AIF were analyzed using Western blot. Neuroprotection was based on levels of apoptosis (TUNEL) and infarct volume (Nissl staining). Immunocytochemistry was used for cellular expression of HSP-70 and pERK 1/2. Significant (P<0.05) up-regulation of HSP-70 and pERK 1/2 after 3 weeks of exercise coincided with significant (P<0.05) reduction in neuronal apoptosis and brain infarct volume. Inhibition of either one of these two factors showed a significant (P<0.05) reversal in the neuroprotection. Bax and AIF were down-regulated, while levels of Bcl-xL were up-regulated in response to stroke after exercise. Inhibiting HSP-70 or pERK 1/2 reversed this resultant increase or decrease. Our results indicate that exercise diminishes neuronal injury in stroke by up-regulating HSP-70 and ERK 1/2.

Original languageEnglish (US)
Pages (from-to)1091-1100
Number of pages10
JournalNeuroscience
Volume166
Issue number4
DOIs
StatePublished - Apr 14 2010

Keywords

  • MCA occlusion
  • anti-apoptotic protein
  • ischemia/reperfusion injury
  • neuroprotection
  • pro-apoptotic protein

ASJC Scopus subject areas

  • Neuroscience(all)

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