Dose-Dependent Protective Effect of Bisperoxovanadium against Acute Cerebral Ischemia in a Rat Model of Ischemia/Reperfusion Injury
PTEN (phosphatase and tensin homologue deleted on chromosome 10) is a dual-specificity lipid and protein phosphatase. The loss of PTEN was originally discovered in numerous human cancers. PTEN inhibition by bisperoxovanadium (bpV) reduces neurological damage after ischemic brain injury. The purpose...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2013-06-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | http://www.mdpi.com/1422-0067/14/6/12013 |
| _version_ | 1811195718220644352 |
|---|---|
| author | Heng-Li Tian Shi-Wen Chen Hao Chen Fang Yuan Jun Ding Jian-Yi Guo |
| author_facet | Heng-Li Tian Shi-Wen Chen Hao Chen Fang Yuan Jun Ding Jian-Yi Guo |
| author_sort | Heng-Li Tian |
| collection | DOAJ |
| description | PTEN (phosphatase and tensin homologue deleted on chromosome 10) is a dual-specificity lipid and protein phosphatase. The loss of PTEN was originally discovered in numerous human cancers. PTEN inhibition by bisperoxovanadium (bpV) reduces neurological damage after ischemic brain injury. The purpose of this study was to identify the optimal neuroprotective dose of bpV when administrated after focal ischemia/reperfusion (I/R) injury in rats. Focal I/R injury was induced using the middle cerebral artery occlusion method. bpV at doses of 0.25, 0.50 and 1.0 mg/kg were injected intraperitoneally just after reperfusion, with saline serving as a vehicle control. A maximal reduction in brain injury was observed with 1.0 mg/kg bpV. This dose of bpV also significantly blocked apoptosis in the penumbral cortex of rats. This beneficial effect was associated with the increasing levels of Akt phosphorylation in the penumbral cortex. These results demonstrate that the pharmacological inhibition of PTEN protects against I/R injury in a dose-dependent manner and the protective effect might be induced through upregulation of the phosphoinositide-3 kinase/Akt pro-survival pathway, suggesting a new therapeutic strategy to combat ischemic brain injury. |
| first_indexed | 2024-04-12T00:47:44Z |
| format | Article |
| id | doaj.art-f930b911eef249e583b1b81a5a5967f4 |
| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-12T00:47:44Z |
| publishDate | 2013-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f930b911eef249e583b1b81a5a5967f42022-12-22T03:54:50ZengMDPI AGInternational Journal of Molecular Sciences1422-00672013-06-01146120131202210.3390/ijms140612013Dose-Dependent Protective Effect of Bisperoxovanadium against Acute Cerebral Ischemia in a Rat Model of Ischemia/Reperfusion InjuryHeng-Li TianShi-Wen ChenHao ChenFang YuanJun DingJian-Yi GuoPTEN (phosphatase and tensin homologue deleted on chromosome 10) is a dual-specificity lipid and protein phosphatase. The loss of PTEN was originally discovered in numerous human cancers. PTEN inhibition by bisperoxovanadium (bpV) reduces neurological damage after ischemic brain injury. The purpose of this study was to identify the optimal neuroprotective dose of bpV when administrated after focal ischemia/reperfusion (I/R) injury in rats. Focal I/R injury was induced using the middle cerebral artery occlusion method. bpV at doses of 0.25, 0.50 and 1.0 mg/kg were injected intraperitoneally just after reperfusion, with saline serving as a vehicle control. A maximal reduction in brain injury was observed with 1.0 mg/kg bpV. This dose of bpV also significantly blocked apoptosis in the penumbral cortex of rats. This beneficial effect was associated with the increasing levels of Akt phosphorylation in the penumbral cortex. These results demonstrate that the pharmacological inhibition of PTEN protects against I/R injury in a dose-dependent manner and the protective effect might be induced through upregulation of the phosphoinositide-3 kinase/Akt pro-survival pathway, suggesting a new therapeutic strategy to combat ischemic brain injury.http://www.mdpi.com/1422-0067/14/6/12013bisperoxovanadiumphosphatase and tensin homologue deleted on chromosome 10cerebral ischemianeuroprotectionAkt |
| spellingShingle | Heng-Li Tian Shi-Wen Chen Hao Chen Fang Yuan Jun Ding Jian-Yi Guo Dose-Dependent Protective Effect of Bisperoxovanadium against Acute Cerebral Ischemia in a Rat Model of Ischemia/Reperfusion Injury International Journal of Molecular Sciences bisperoxovanadium phosphatase and tensin homologue deleted on chromosome 10 cerebral ischemia neuroprotection Akt |
| title | Dose-Dependent Protective Effect of Bisperoxovanadium against Acute Cerebral Ischemia in a Rat Model of Ischemia/Reperfusion Injury |
| title_full | Dose-Dependent Protective Effect of Bisperoxovanadium against Acute Cerebral Ischemia in a Rat Model of Ischemia/Reperfusion Injury |
| title_fullStr | Dose-Dependent Protective Effect of Bisperoxovanadium against Acute Cerebral Ischemia in a Rat Model of Ischemia/Reperfusion Injury |
| title_full_unstemmed | Dose-Dependent Protective Effect of Bisperoxovanadium against Acute Cerebral Ischemia in a Rat Model of Ischemia/Reperfusion Injury |
| title_short | Dose-Dependent Protective Effect of Bisperoxovanadium against Acute Cerebral Ischemia in a Rat Model of Ischemia/Reperfusion Injury |
| title_sort | dose dependent protective effect of bisperoxovanadium against acute cerebral ischemia in a rat model of ischemia reperfusion injury |
| topic | bisperoxovanadium phosphatase and tensin homologue deleted on chromosome 10 cerebral ischemia neuroprotection Akt |
| url | http://www.mdpi.com/1422-0067/14/6/12013 |
| work_keys_str_mv | AT henglitian dosedependentprotectiveeffectofbisperoxovanadiumagainstacutecerebralischemiainaratmodelofischemiareperfusioninjury AT shiwenchen dosedependentprotectiveeffectofbisperoxovanadiumagainstacutecerebralischemiainaratmodelofischemiareperfusioninjury AT haochen dosedependentprotectiveeffectofbisperoxovanadiumagainstacutecerebralischemiainaratmodelofischemiareperfusioninjury AT fangyuan dosedependentprotectiveeffectofbisperoxovanadiumagainstacutecerebralischemiainaratmodelofischemiareperfusioninjury AT junding dosedependentprotectiveeffectofbisperoxovanadiumagainstacutecerebralischemiainaratmodelofischemiareperfusioninjury AT jianyiguo dosedependentprotectiveeffectofbisperoxovanadiumagainstacutecerebralischemiainaratmodelofischemiareperfusioninjury |