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Reversal of postischemic hypoperfusion by tempol: endothelial signal transduction mechanism.
- Source :
-
Neurochemical research [Neurochem Res] 2012 Apr; Vol. 37 (4), pp. 680-8. Date of Electronic Publication: 2011 Dec 03. - Publication Year :
- 2012
-
Abstract
- This report entails in vivo and in vitro studies concerned with free radical species involved in brain ischemia. The participation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the early manifestation of cerebral ischemia/reperfusion was investigated in gerbils exposed to transient global ischemia using 4-OH-2,2,6,6-tetramethylpiperidine-1-oxyl (TPL), a well-known antioxidant. TPL treatment reversed cerebral postischemic hypoperfusion and tissue edema in these animals. The findings are consistent with ROS/RNS participation in tissue injury and the reduction of cerebromicrovascular blood flow (CBF) during postischemic recirculation. The activation/deactivation of signal transduction pathway by oxidation/antioxidation [i.e., using hydrogen peroxide (H₂O₂)/TPL] was evaluated in cultured human brain endothelial cells (HBEC) to assess the involvement of endothelial-dependent mechanisms. The data showed that H₂O₂ activates various "stress" kinases and vasodilalator-stimulated phosphoprotein (VASP); activation of this pathway was reduced by inhibitors of Rho- or IP-3 kinases, as well as TPL. H₂O₂ also induced cytoskeleton (actin) rearrangements in HBEC; this effect was prevented by inhibitors of Rho/IP3 kinase or TPL. The observed activation/deactivation of H₂O₂-induced "stress" kinase is in agreement with the reported capacity of ROS/RNS to stimulate the oxidative signal transduction pathway. The noted TPL reduction of H₂O₂-induced phosphorylation of kinase strongly suggests that the beneficial effect of TPL implicates the stress signal transduction pathway. This may represent a mechanism for the cerebral postischemic manifestations observed by in vivo experiments.
- Subjects :
- Animals
Antioxidants pharmacology
Brain Ischemia drug therapy
Cells, Cultured
Endothelium, Vascular drug effects
Gerbillinae
Humans
Oxidative Stress drug effects
Oxidative Stress physiology
Reactive Oxygen Species metabolism
Signal Transduction drug effects
Spin Labels
Antioxidants therapeutic use
Brain Ischemia metabolism
Cyclic N-Oxides pharmacology
Cyclic N-Oxides therapeutic use
Endothelium, Vascular physiology
Signal Transduction physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1573-6903
- Volume :
- 37
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Neurochemical research
- Publication Type :
- Academic Journal
- Accession number :
- 22139482
- Full Text :
- https://doi.org/10.1007/s11064-011-0595-y