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The Akt/GSK-3β pathway mediates flurbiprofen-induced neuroprotection against focal cerebral ischemia/reperfusion injury in rats.
Biochem Biophys Res Commun. 2011 Jun 17; 409(4):808-13.BB

Abstract

Apoptosis is one of the major mechanisms of cell death during cerebral ischemia and reperfusion injury. Flurbiprofen has been shown to reduce cerebral ischemia/reperfusion injury in both focal and global cerebral ischemia models, but the mechanism remains unclear. This study aimed to investigate the potential association between the neuroprotective effect of flurbiprofen and the apoptosis inhibiting signaling pathways, in particularly the Akt/GSK-3β pathway. A focal cerebral ischemia rat model was subjected to middle cerebral artery occlusion (MCAO) for 120 min and then treated with flurbiprofen at the onset of reperfusion. The infarct volume and the neurological deficit scores were evaluated at 24h after reperfusion. Cell apoptosis, apoptosis-related proteins and the levels of p-Akt and p-GSK-3β in ischemic penumbra were measured using TUNEL and western blot. The results showed that administration of flurbiprofen at the doses of 5 and 10mg/kg significantly attenuated brain ischemia/reperfusion injury, as shown by a reduction in the infarct volume, neurological deficit scores and cell apoptosis. Moreover, flurbiprofen not only inhibited the expression of Bax protein and p-GSK-3β, but also increased the expression of Bcl-2 protein, the ratio of Bcl-2/Bax as well as the P-Akt level. Taken together, these results suggest that flurbiprofen protects the brain from ischemia/reperfusion injury by reducing apoptosis and this neuroprotective effect may be partly due to the activation of Akt/GSK-3β signaling pathway.

Authors+Show Affiliations

Department of Pharmacology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21624354

Citation

Sun, Baozhu, et al. "The Akt/GSK-3β Pathway Mediates Flurbiprofen-induced Neuroprotection Against Focal Cerebral Ischemia/reperfusion Injury in Rats." Biochemical and Biophysical Research Communications, vol. 409, no. 4, 2011, pp. 808-13.
Sun B, Chen L, Wei X, et al. The Akt/GSK-3β pathway mediates flurbiprofen-induced neuroprotection against focal cerebral ischemia/reperfusion injury in rats. Biochem Biophys Res Commun. 2011;409(4):808-13.
Sun, B., Chen, L., Wei, X., Xiang, Y., Liu, X., & Zhang, X. (2011). The Akt/GSK-3β pathway mediates flurbiprofen-induced neuroprotection against focal cerebral ischemia/reperfusion injury in rats. Biochemical and Biophysical Research Communications, 409(4), 808-13. https://doi.org/10.1016/j.bbrc.2011.05.095
Sun B, et al. The Akt/GSK-3β Pathway Mediates Flurbiprofen-induced Neuroprotection Against Focal Cerebral Ischemia/reperfusion Injury in Rats. Biochem Biophys Res Commun. 2011 Jun 17;409(4):808-13. PubMed PMID: 21624354.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Akt/GSK-3β pathway mediates flurbiprofen-induced neuroprotection against focal cerebral ischemia/reperfusion injury in rats. AU - Sun,Baozhu, AU - Chen,Lin, AU - Wei,Xinbing, AU - Xiang,Yanxiao, AU - Liu,Xiaoqian, AU - Zhang,Xiumei, Y1 - 2011/05/23/ PY - 2011/05/08/received PY - 2011/05/14/accepted PY - 2011/6/1/entrez PY - 2011/6/1/pubmed PY - 2011/9/3/medline SP - 808 EP - 13 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 409 IS - 4 N2 - Apoptosis is one of the major mechanisms of cell death during cerebral ischemia and reperfusion injury. Flurbiprofen has been shown to reduce cerebral ischemia/reperfusion injury in both focal and global cerebral ischemia models, but the mechanism remains unclear. This study aimed to investigate the potential association between the neuroprotective effect of flurbiprofen and the apoptosis inhibiting signaling pathways, in particularly the Akt/GSK-3β pathway. A focal cerebral ischemia rat model was subjected to middle cerebral artery occlusion (MCAO) for 120 min and then treated with flurbiprofen at the onset of reperfusion. The infarct volume and the neurological deficit scores were evaluated at 24h after reperfusion. Cell apoptosis, apoptosis-related proteins and the levels of p-Akt and p-GSK-3β in ischemic penumbra were measured using TUNEL and western blot. The results showed that administration of flurbiprofen at the doses of 5 and 10mg/kg significantly attenuated brain ischemia/reperfusion injury, as shown by a reduction in the infarct volume, neurological deficit scores and cell apoptosis. Moreover, flurbiprofen not only inhibited the expression of Bax protein and p-GSK-3β, but also increased the expression of Bcl-2 protein, the ratio of Bcl-2/Bax as well as the P-Akt level. Taken together, these results suggest that flurbiprofen protects the brain from ischemia/reperfusion injury by reducing apoptosis and this neuroprotective effect may be partly due to the activation of Akt/GSK-3β signaling pathway. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/21624354/The_Akt/GSK_3β_pathway_mediates_flurbiprofen_induced_neuroprotection_against_focal_cerebral_ischemia/reperfusion_injury_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(11)00862-X DB - PRIME DP - Unbound Medicine ER -