Delayed administration of parecoxib, a specific COX-2 inhibitor, attenuated postischemic neuronal apoptosis by phosphorylation Akt and GSK-3β.

Abstract

Parecoxib is a recently described novel COX-2 inhibitor whose functional significance and neuroprotective mechanisms remain elusive. Therefore, in this study, we aimed to investigate whether delayed administration of parecoxib inhibited mitochondria-mediated neuronal apoptosis induced by ischemic reperfusion injury via phosphorylating Akt and its downstream target protein, glycogen synthase kinase 3β (GSK-3β). Adult male Sprague-Dawley rats were administered parecoxib (10 or 30 mg kg(-1), IP) or isotonic saline twice a day starting 24 h after middle cerebral artery occlusion (MCAO) for three consecutive days. Cerebral infarct volume, apoptotic neuron, caspase-3 immunoreactivity and the protein expression of p-Akt, p-GSK-3β and Cytochrome C in cerebral ischemic cortex were evaluated at 96 h after reperfusion. Parecoxib significantly diminished infarct volume and attenuated neuron apoptosis in a dose-independent manner, compared with MCAO group alone. Increased p-Akt and p-GSK-3β was observed in the ischemic penumbra of parecoxib group after stroke. Moreover, parecoxib also reduced the release of Cytochrome C from mitochondrial into cytosol and attenuated the caspase-3 immunoreactivity in the penumbra. Taken together, these results suggested that parecoxib ameliorated postischemic mitochondria-mediated neuronal apoptosis induced by focal cerebral ischemia in rats and this neuroprotective potential is involved in phosphorylation of Akt and GSK-3β.

• Authors: Zhi Ye, Na Wang, Pingping Xia, E Wang, Yajing Yuan, Qulian Guo
• Journal: Neurochemical research (Neurochem Res) Vol. 37 Issue 2 Pg. 321-9 (Feb 2012) ISSN: 1573-6903 [Electronic] United States
• PMID: 21964800 (Publication Type: Journal Article)

Chemical References

• Cyclooxygenase 2 Inhibitors
• Isoxazoles
• parecoxib
• Glycogen Synthase Kinase 3 beta
• Gsk3b protein, rat
• Proto-Oncogene Proteins c-akt
• Glycogen Synthase Kinase 3

Topics

• Animals
• Apoptosis (drug effects)
• Blotting, Western
• Cyclooxygenase 2 Inhibitors (administration & dosage, pharmacology)
• Glycogen Synthase Kinase 3 (metabolism)
• Glycogen Synthase Kinase 3 beta
• In Situ Nick-End Labeling
• Ischemia (pathology)
• Isoxazoles (administration & dosage, pharmacology)
• Male
• Neurons (drug effects)
• Phosphorylation
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats
• Rats, Sprague-Dawley