Neuroprotective effect of phosphatase and tensin homolog allele activity deleted in chromosome 10 inhibition on neuronal apoptosis after hypoxia-ischemia
10.3760/cma.j.issn.2095-428X.2013.24.006
- VernacularTitle:抑制第10号染色体缺失的磷酸酶和张力蛋白同源等位基因活性对缺氧缺血神经元凋亡的保护作用
- Author:
Jing ZHAO
1
;
Yi QU
;
De-Zhi MU
Author Information
1. 四川大学华西第二医院儿科
- Keywords:
Phosphatase and tensin homolog deleted in chromosome 10;
Protein kinase B;
Glycogen synthasekinase-3β;
Myeloid cell leukemia-1;
Apoptosis;
Neuron;
Hypoxia-ischemia
- From:
Chinese Journal of Applied Clinical Pediatrics
2013;28(24):1855-1859
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanisms of neuroprotective roles of phosphatase and tensin homolog allele activity deleted in chromosome 10 (PTEN) inhibition on neuronal apoptosis after hypoxia-ischemia (HI)damage.Methods The cerebral cortical neurons of newbom Sprague-Dawley rats were cultured in vitro.Oxygen and glucose deprivation (OGD) model was established to imitate HI environment in vivo.Neurons were divided randomly into 3 groups:control group:neurons were treated with normal medium ; OGD group:neurons were treated with OGD for 3 h followed by reperfusion at 0.5,3.0,6.0,12.0,24.0,48.0 h ; PTEN inhibition group:before OGD treatment,neurons were pretreated with PTEN inhibitor,and then the neurons were collected at 24 h after reperfusion.Terminal deoxynucleotidyl transferase-mediated dUTP nick and labeling staining was used to detect the apoptotic cells.Western blot was used to detect the expression of PTEN,p-PTEN,protein kinase B(Akt),p-Akt,synthesis of glucose kinase-3 betal (GSK-3β),p-GSK-3β and myeloid cell ceukemia-1 (Mcl-1).Results 1.As compared with control group,TUNEL positive cells increased after OGD observed by TUNEL staining (P ＜ 0.05).The expression of PTEN was increased,the expressions of p-PTEN,p-Akt,p-GSK-3 β,and Mcl-1 were significantly decreased after OGD (all P ＜ 0.05).However,Akt and GSK-3β remained unchanged at different time points after OGD(all P ＞ 0.05).2.As compared with OGD group,TUNEL positive cells were obviously reduced at 24 h after OGD in PTEN group (P ＜ 0.05).Although total PTEN,Akt,and GSK-3 β were not obviously changed in PTEN group(all P ＞ 0.05),the expressions of p-PTEN,p-Akt,p-GSK-3β,and Mcl-1 were significantly increased after OGD (all P ＜ 0.05).Conclusions HI can induce neuronal apoptosis,and the mechanisms of apoptosis may involve PTEN/Akt/GSK-3β/Mcl-1 pathway.The phosphorylation of Akt and GSK-3β can be increased via PTEN activity inhibition,while the ubiquitination of Mcl-1 would be decreased,and thus reduce the neuronal apoptosis.
