Geranylgeranylacetone attenuates cerebral ischemia–reperfusion injury in rats through the augmentation of HSP 27 phosphorylation: a preliminary study
Abstract Background We 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–reperf...
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| Language: | English |
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BMC
2021-02-01
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| Series: | BMC Neuroscience |
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| Online Access: | https://doi.org/10.1186/s12868-021-00614-7 |
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| author | Kazuya Matsuo Kohkichi Hosoda Jun Tanaka Yusuke Yamamoto Taichiro Imahori Tomoaki Nakai Yasuhiro Irino Masakazu Shinohara Takashi Sasayama Eiji Kohmura |
| author_facet | Kazuya Matsuo Kohkichi Hosoda Jun Tanaka Yusuke Yamamoto Taichiro Imahori Tomoaki Nakai Yasuhiro Irino Masakazu Shinohara Takashi Sasayama Eiji Kohmura |
| author_sort | Kazuya Matsuo |
| collection | DOAJ |
| description | Abstract Background We 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. Methods In 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. Results Pathway 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). Conclusions As 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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| format | Article |
| id | doaj.art-8e39a716f0bf49748daf8f5cd54b0fb8 |
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| language | English |
| last_indexed | 2024-12-17T05:40:13Z |
| publishDate | 2021-02-01 |
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| spelling | doaj.art-8e39a716f0bf49748daf8f5cd54b0fb82022-12-21T22:01:28ZengBMCBMC Neuroscience1471-22022021-02-0122111110.1186/s12868-021-00614-7Geranylgeranylacetone attenuates cerebral ischemia–reperfusion injury in rats through the augmentation of HSP 27 phosphorylation: a preliminary studyKazuya Matsuo0Kohkichi Hosoda1Jun Tanaka2Yusuke Yamamoto3Taichiro Imahori4Tomoaki Nakai5Yasuhiro Irino6Masakazu Shinohara7Takashi Sasayama8Eiji Kohmura9Department of Neurosurgery, Kobe University Graduate School of MedicineDepartment of Neurosurgery, Kobe City Nishi-Kobe Medical CenterDepartment of Neurosurgery, Konan HospitalDepartment of Neurosurgery, Toyooka HospitalDepartment of Neurosurgery, Hyogo Brain and Heart Center at HimejiDepartment of Neurosurgery, Kobe University Graduate School of MedicineDivision of Evidence-based Laboratory Medicine, Kobe University Graduate School of MedicineDivision of Medical Education, Kobe University Graduate School of MedicineDepartment of Neurosurgery, Kobe University Graduate School of MedicineDepartment of Neurosurgery, Kobe University Graduate School of MedicineAbstract Background We 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. Methods In 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. Results Pathway 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). Conclusions As 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.https://doi.org/10.1186/s12868-021-00614-7Glucose-6-phosphate dehydrogenaseHeat shock proteinMetabolomicsOxidative stressReperfusion injuryStroke |
| spellingShingle | Kazuya Matsuo Kohkichi Hosoda Jun Tanaka Yusuke Yamamoto Taichiro Imahori Tomoaki Nakai Yasuhiro Irino Masakazu Shinohara Takashi Sasayama Eiji Kohmura Geranylgeranylacetone attenuates cerebral ischemia–reperfusion injury in rats through the augmentation of HSP 27 phosphorylation: a preliminary study BMC Neuroscience Glucose-6-phosphate dehydrogenase Heat shock protein Metabolomics Oxidative stress Reperfusion injury Stroke |
| title | Geranylgeranylacetone attenuates cerebral ischemia–reperfusion injury in rats through the augmentation of HSP 27 phosphorylation: a preliminary study |
| title_full | Geranylgeranylacetone attenuates cerebral ischemia–reperfusion injury in rats through the augmentation of HSP 27 phosphorylation: a preliminary study |
| title_fullStr | Geranylgeranylacetone attenuates cerebral ischemia–reperfusion injury in rats through the augmentation of HSP 27 phosphorylation: a preliminary study |
| title_full_unstemmed | Geranylgeranylacetone attenuates cerebral ischemia–reperfusion injury in rats through the augmentation of HSP 27 phosphorylation: a preliminary study |
| title_short | Geranylgeranylacetone attenuates cerebral ischemia–reperfusion injury in rats through the augmentation of HSP 27 phosphorylation: a preliminary study |
| title_sort | geranylgeranylacetone attenuates cerebral ischemia reperfusion injury in rats through the augmentation of hsp 27 phosphorylation a preliminary study |
| topic | Glucose-6-phosphate dehydrogenase Heat shock protein Metabolomics Oxidative stress Reperfusion injury Stroke |
| url | https://doi.org/10.1186/s12868-021-00614-7 |
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