title: 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.
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-x(L), 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-x(L), 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-x(L) 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.
authors.affiliation: Department of Neurosurgery, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors.forename: B
authors.initials: B
authors.lastname: Liebelt
authors.forename: P
authors.initials: P
authors.lastname: Papapetrou
authors.forename: A
authors.initials: A
authors.lastname: Ali
authors.forename: M
authors.initials: M
authors.lastname: Guo
authors.forename: X
authors.initials: X
authors.lastname: Ji
authors.forename: C
authors.initials: C
authors.lastname: Peng
authors.forename: R
authors.initials: R
authors.lastname: Rogers
authors.forename: A
authors.initials: A
authors.lastname: Curry
authors.forename: D
authors.initials: D
authors.lastname: Jimenez
authors.forename: Y
authors.initials: Y
authors.lastname: Ding
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D020520:Brain Infarction / Q000503:physiopathology / Q000517:prevention & control / Q000628:therapy; D019610:Cytoprotection / Q000502:physiology; D004195:Disease Models, Animal; D005081:Exercise Therapy / Q000379:methods; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009410:Nerve Degeneration / Q000503:physiopathology / Q000517:prevention & control / Q000628:therapy*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D020521:Stroke / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D051017:Apoptosis Regulatory Proteins; D018840:HSP70 Heat-Shock Proteins; D048052:Mitogen-Activated Protein Kinase 3