Abstract | BACKGROUND AND PURPOSE: METHODS: RESULTS: Our results revealed that IPostC relieved transient middle cerebral artery occlusion-induced oxidative damage by reducing reactive oxygen species, malondialdehyde, and 3-nitrotyrosine accumulation in the peri- infarct cortex and raised levels of antioxidants perioxiredoxin-1, peroxiredoxin-2, and thioredoxin-1. In addition, IPostC increased p-AKT and p-TOPK levels, which colocalized in neural cells. In vitro TOPK knockdown by small interfering RNA decreased the levels of antioxidants peroxiredoxin-1, thioredoxin, and manganese superoxide dismutase activity in PC12 cells. In vivo intracerebroventricular injection of TOPK small interfering RNA reversed IPostC-induced neuroprotection by increasing infarct volume and nitric oxide content and reducing manganese superoxide dismutase activity. Moreover, IPostC-evoked Akt activation was blocked by TOPK small interfering RNA in vivo, but the decreased phosphorylated phosphatase and tensin homolog level in ischemia/reperfusion was not influenced by IPostC or by TOPK small interfering RNA treatment. CONCLUSIONS: Our results suggest that the antioxidative effects of TOPK/Akt might contribute to the neuroprotection of IPostC treatment against transient middle cerebral artery occlusion.
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Authors | Haiping Zhao, Rongliang Wang, Zhen Tao, Li Gao, Feng Yan, Zhi Gao, Xiangrong Liu, Xunming Ji, Yumin Luo |
Journal | Stroke
(Stroke)
Vol. 45
Issue 8
Pg. 2417-24
(Aug 2014)
ISSN: 1524-4628 [Electronic] United States |
PMID | 25013016
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2014 American Heart Association, Inc. |
Chemical References |
- Reactive Oxygen Species
- Superoxides
- Malondialdehyde
- Proto-Oncogene Proteins c-akt
- Mitogen-Activated Protein Kinase Kinases
- PDZ-binding kinase
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Topics |
- Animals
- Brain
(metabolism)
- Brain Ischemia
(metabolism)
- Ischemic Postconditioning
- Lipid Peroxidation
(physiology)
- Malondialdehyde
(metabolism)
- Mitogen-Activated Protein Kinase Kinases
(metabolism)
- Phosphorylation
- Proto-Oncogene Proteins c-akt
(metabolism)
- Rats
- Reactive Oxygen Species
(metabolism)
- Reperfusion Injury
(metabolism, prevention & control)
- Signal Transduction
(physiology)
- Superoxides
(metabolism)
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