Abstract
BackgroundSevoflurane preconditioning induces brain ischemic tolerance, but the mechanism remains poorly elucidated. Nitration is an important form of post-translational modification in pathological signaling. This study was to investigate the role of thioredoxin-1 (Trx-1) nitration in neuroprotection effect induced by sevoflurane preconditioning in a transient stroke model in rats.MethodsAdult male Sprague–Dawley rats were preconditioned with 2% sevoflurane or vehicle oxygen exposure, 1 h per day, for 5 consecutive days. At 24 h after the last exposure, rats were subjected to focal brain ischemia induced by middle cerebral artery occlusion (MCAO) for 90 min, followed by 72-h reperfusion. Trx-1 expression and activity, as well as the content of nitrotyrosine at penumbra were detected at 24 h after preconditioning and 2, 8, 24, 72 h after MCAO. Nitrated Trx-1 was examined by immunoprecipitation at 8 h after MCAO. The role of Trx-1 nitration in ischemic tolerance was assessed by administration of nitrated human-Trx-1 prior to MCAO. Neurological scores, brain infarct volumes and TUNEL staining were evaluated at 24 h after reperfusion.ResultsIschemic stroke decreased Trx-1 activity but not the expression in penumbra tissue. The content of nitrotyrosine was elevated after MCAO. Preconditioning with sevoflurane increased Trx-1 activity and reduced its nitration at 8 h after MCAO in comparison with vehicle preconditioning. The decrement of Trx-1 activity was correlated with its nitration level. Exogenous administration of nitrated human-Trx-1 reversed the brain ischemic tolerance of sevoflurane preconditioning, exacerbating brain infarct volume, neurobehavioral defects and apoptosis, while administration of human-Trx-1 had no effect on the sevoflurane preconditioning-induced neuroprotection.ConclusionIschemic stroke reduces Trx-1 activity via post-translational nitrative modulation in rats. Sevoflurane preconditioning induces brain ischemic tolerance and anti-apoptosis by partially preserving Trx-1 activity via inhibiting nitration.
Highlights
Sevoflurane preconditioning induces brain ischemic tolerance, but the mechanism remains poorly elucidated
Sevoflurane preconditioning increased the activity but not the expression of Trx-1 To understand the role of Trx-1 in the sevoflurane preconditioning-induced neuroprotection, we observed the activity changes of Trx-1 after brain ischemic stroke
There was a significant increase of Trx-1 activity in sevoflurane-preconditioned rats compared with those in vehicle group at 8 h after ischemia insult (0.63 ± 0.06 vs. 0.36 ± 0.04, Sevoflurane group (Sev) middle cerebral artery occlusion (MCAO) 8 h vs. Oxygen group (Oxy) MCAO 8 h, P < 0.05)
Summary
Sevoflurane preconditioning induces brain ischemic tolerance, but the mechanism remains poorly elucidated. Nitration is an important form of post-translational modification in pathological signaling. This study was to investigate the role of thioredoxin-1 (Trx-1) nitration in neuroprotection effect induced by sevoflurane preconditioning in a transient stroke model in rats. Preconditioning with volatile anesthetics induces tolerance to cerebral ischemia/reperfusion injury in animals, and prevents neurologic complications such as perioperative stroke in patients [1]. The anti-oxidation and anti-apoptosis are the most important underlying pathways associated with the preconditioning-elicited neuroprotection, in which the activation of many signaling molecules and enzymes are altered directly or indirectly by the preconditioning interventions [3, 4]. Extensive evidences have indicated that protein nitration is an important form of post-translational modification in pathological. Interventions that modulate post-translational modification of protein have been proposed in the treatment of ischemia [5]
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