Mechanism of ischemic postconditioning regulated Akt(pS473) and Akt(pT308) hyperphosphorylation and neuronal apoptosis in hippocampal CA1 area after cerebral ischemia in tree shrew
Author(s): TANG Yang, LI Shu-qing, Department of Dermatology, the First Affiliated Hospital, Kunming Medical University, Department of Pathophysiology, Kunming Medical University
Pages: 591-598
Year: 2016 Issue: 5
Journal: Acta Anatomica Sinica
Keyword: Cerebral ischemia; Postconditioning; Hippocampus; Akt phosphorylation; Signal transduction; Photochemistry; Tree shrew;
Abstract: Objective To investigate the effects of Akt( p S473) and( p T308) phosphorylation on neurons apoptosis in hippocampal CA1 area after thrombotic cerebral ischemia, and to explore the possible mechanisms of ischemic postconditioning( PC) for inhibiting neuron apoptosis. Methods Thrombotic cerebral ischemia was induced by photochemical reaction and an ischemic PC model was established in tree shrews. The expression and phosphorylation of Akt( p S473) and Akt( p T308) in hippocampus CA1 area were determined,respectively,by immunohistochemistry and ELISA. The neuron apoptosis was detected by a kits-detection of immunohistochemistry TACS in situ. Ultrastructures of cortex and hippocampal neurons were abserved under an electron microscope. Results The neurons shrinkaged,nuclear disappear in 24 hours after cerebral ischemia. The expression and phosphorylation levels of Akt( p S473) and Akt( p T308) in hippocampal CA1 area were significantly higher [Akt( p S473) :( 152. 3 ± 3. 5) units / mg,( 130. 8 ± 2. 6) units / mg and( 149. 5 ± 4. 7) units/mg and AKT( p T308) :( 42. 35 ± 2. 49) units/mg,( 19. 23 ± 1. 41) units/mg and( 23. 38 ± 1. 32)units / mg,respectively,( P < 0. 01) ] than the control group,and the counts of TUNEL positive cells in hippocampal CA1 area were increased significantly than the control group( P < 0. 01) in the ischemic group in different time points,but theless TUNEL positive neurons decreased significantly( P < 0. 01). Neuron injury was reduced significantly in the ischemia PC group,and this change coincided with the level of Akt( p S473) and Akt( p T308) activation. Conclusion The level of phosphorylation of Akt( p S473) and Akt( p T308) is closely related to the neuron apoptosis of hippocampal CA1 area after brain ischemia in tree shrews,and the mutual phosphorylation of Akt( p S473) and Akt[p T308]exerts an important role in inhibition of hippocampal cell apoptosis after ischemic PC treatment.
Pages: 591-598
Year: 2016 Issue: 5
Journal: Acta Anatomica Sinica
Keyword: Cerebral ischemia; Postconditioning; Hippocampus; Akt phosphorylation; Signal transduction; Photochemistry; Tree shrew;
Abstract: Objective To investigate the effects of Akt( p S473) and( p T308) phosphorylation on neurons apoptosis in hippocampal CA1 area after thrombotic cerebral ischemia, and to explore the possible mechanisms of ischemic postconditioning( PC) for inhibiting neuron apoptosis. Methods Thrombotic cerebral ischemia was induced by photochemical reaction and an ischemic PC model was established in tree shrews. The expression and phosphorylation of Akt( p S473) and Akt( p T308) in hippocampus CA1 area were determined,respectively,by immunohistochemistry and ELISA. The neuron apoptosis was detected by a kits-detection of immunohistochemistry TACS in situ. Ultrastructures of cortex and hippocampal neurons were abserved under an electron microscope. Results The neurons shrinkaged,nuclear disappear in 24 hours after cerebral ischemia. The expression and phosphorylation levels of Akt( p S473) and Akt( p T308) in hippocampal CA1 area were significantly higher [Akt( p S473) :( 152. 3 ± 3. 5) units / mg,( 130. 8 ± 2. 6) units / mg and( 149. 5 ± 4. 7) units/mg and AKT( p T308) :( 42. 35 ± 2. 49) units/mg,( 19. 23 ± 1. 41) units/mg and( 23. 38 ± 1. 32)units / mg,respectively,( P < 0. 01) ] than the control group,and the counts of TUNEL positive cells in hippocampal CA1 area were increased significantly than the control group( P < 0. 01) in the ischemic group in different time points,but theless TUNEL positive neurons decreased significantly( P < 0. 01). Neuron injury was reduced significantly in the ischemia PC group,and this change coincided with the level of Akt( p S473) and Akt( p T308) activation. Conclusion The level of phosphorylation of Akt( p S473) and Akt( p T308) is closely related to the neuron apoptosis of hippocampal CA1 area after brain ischemia in tree shrews,and the mutual phosphorylation of Akt( p S473) and Akt[p T308]exerts an important role in inhibition of hippocampal cell apoptosis after ischemic PC treatment.
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