Geranylgeranylacetone protects against cerebral ischemia and reperfusion injury: HSP90 and eNOS phosphorylation involved.

Abstract

Cerebral ischemia and reperfusion (I/R) can trigger a cytotoxic cascade with overflow of reactive oxygen species, paradoxically causing neurological dysfunction, redox imbalance, inflammation and apoptosis. The present study aims to investigate the effect of geranylgeranylacetone(GGA) on cerebral I/R injury and the underlying mechanism. The results demonstrated that cerebral I/R increased the neurological function abnormality, brain edema, inflammation and oxidative injury in rats as well as the cognitive impairment, which was significantly reversed by GGA in a dose-dependent manner. GGA also suppressed the cell injury and apoptosis caused by cerebral I/R. Moreover, the protective effect of GGA was found to involve heat shock protein 90 (HSP90) and phosphorylated endothelial nitric oxide synthase (eNOS) expression and activity. Both the HSP90 and eNOS inhibitor abolished the effect of GGA. The data showed that GGA could protect rats against cerebral I/R injury, which may be related to the induction of HSP90 and activation of eNOS.

• Authors: Dake He, Xiaoqing Song, Ling Li
• Journal: Brain research (Brain Res) Vol. 1599 Pg. 150-7 (Mar 02 2015) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 25514333 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Diterpenes
• HSP90 Heat-Shock Proteins
• Neuroprotective Agents
• Tumor Necrosis Factor-alpha
• Malondialdehyde
• Nitric Oxide Synthase Type III
• Nos3 protein, rat
• geranylgeranylacetone

Topics

• Animals
• Apoptosis (drug effects, physiology)
• Brain (drug effects, pathology, physiopathology)
• Brain Edema (drug therapy, pathology, physiopathology)
• Brain Ischemia (drug therapy, pathology, physiopathology)
• Cognition Disorders (drug therapy, pathology, physiopathology)
• Disease Models, Animal
• Diterpenes (pharmacology)
• HSP90 Heat-Shock Proteins (antagonists & inhibitors, metabolism)
• Malondialdehyde (metabolism)
• Maze Learning (drug effects, physiology)
• Neuroimmunomodulation (drug effects, physiology)
• Neuroprotective Agents (pharmacology)
• Nitric Oxide Synthase Type III (antagonists & inhibitors, metabolism)
• Phosphorylation (drug effects)
• Random Allocation
• Rats, Sprague-Dawley
• Reperfusion Injury (drug therapy, pathology, physiopathology)
• Treatment Outcome
• Tumor Necrosis Factor-alpha (metabolism)