ArticleBMC neuroscience2021
Geranylgeranylacetone attenuates cerebral ischemia-reperfusion injury in rats through the augmentation of HSP 27 phosphorylation: a preliminary study.
Article in BMC neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 8 citations in OpenAlex.
- Pentose Phosphate Pathway Is Critical for Providing Energy by Bypassing 6-Phosphofructo-1-Kinase (PFK1) During Increased Neuronal Activity.Metabolites · 2026Review
- MK5 Regulates Microglial Activation and Neuroinflammation in Experimental Stroke Models.CNS neuroscience & therapeutics · 2025Article
- Advances of Oxidative Stress Impact in Periodontitis: Biomarkers and Effective Targeting Options.Current medicinal chemistry · 2024Review
- Mechanistic insights into heat shock protein 27, a potential therapeutic target for cardiovascular diseases.Frontiers in cardiovascular medicine · 2023Review
- Role of oxidative stress in the relationship between periodontitis and systemic diseases.Frontiers in physiology · 2023Review
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundWe previously reported that heat shock protein 27 (HSP27) phosphorylation plays an important role in the activation of glucose-6-phosphate dehydrogenase (G6PD), resulting in the upregulation of the pentose phosphate pathway and antioxidant effects against cerebral ischemia-reperfusion injury. The present study investigated the effect of geranylgeranylacetone, an inducer of HSP27, on ischemia-reperfusion injury in male rats as a preliminary study to see if further research of the effects of geranylgeranylacetone on the ischemic stroke was warranted.
methodsIn all experiments, male Wistar rats were used. First, we conducted pathway activity profiling based on a gas chromatography-mass spectrometry to identify ischemia-reperfusion-related metabolic pathways. Next, we investigated the effects of geranylgeranylacetone on the pentose phosphate pathway and ischemia-reperfusion injury by real-time polymerase chain reaction (RT-PCR), immunoblotting, and G6PD activity, protein carbonylation and infarct volume analysis. Geranylgeranylacetone or vehicle was injected intracerebroventricularly 3 h prior to middle cerebral artery occlusion or sham operation.
resultsPathway activity profiling demonstrated that changes in the metabolic state depended on reperfusion time and that the pentose phosphate pathway and taurine-hypotaurine metabolism pathway were the most strongly related to reperfusion among 137 metabolic pathways. RT-PCR demonstrated that geranylgeranylacetone did not significantly affect the increase in HSP27 transcript levels after ischemia-reperfusion. Immunoblotting showed that geranylgeranylacetone did not significantly affect the elevation of HSP27 protein levels. However, geranylgeranylacetone significantly increase the elevation of phosphorylation of HSP27 after ischemia-reperfusion. In addition, geranylgeranylacetone significantly affected the increase in G6PD activity, and reduced the increase in protein carbonylation after ischemia-reperfusion. Accordingly, geranylgeranylacetone significantly reduced the infarct size (median 31.3% vs 19.9%, p = 0.0013).
conclusionsAs a preliminary study, these findings suggest that geranylgeranylacetone may be a promising agent for the treatment of ischemic stroke and would be worthy of further study. Further studies are required to clearly delineate the mechanism of geranylgeranylacetone-induced HSP27 phosphorylation in antioxidant effects, which may guide the development of new approaches for minimizing the impact of cerebral ischemia-reperfusion injury.
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