Open AccessProgesterone alleviates hypoxic-ischemic brain injury via the Akt/GSK-3β signaling pathway
Author(s) -
Xiaojuan Li,
Junhe Zhang,
Shujie Chai,
Xiaoyin Wang
Publication year - 2014
Publication title -
experimental and therapeutic medicine
Language(s) - English
Resource type - Journals
eISSN - 1792-1015
pISSN - 1792-0981
DOI - 10.3892/etm.2014.1858
Subject(s) - protein kinase b , wortmannin , gsk 3 , pi3k/akt/mtor pathway , apoptosis , gsk3b , western blot , glycogen synthase , biology , signal transduction , endocrinology , kinase , medicine , chemistry , phosphorylation , microbiology and biotechnology , biochemistry , gene
This aim of this study was to investigate whether progesterone (PROG) alleviates the neuronal apoptosis in neonatal rats with hypoxic-ischemic (HI) brain damage through the phosphatidylinositol 3-kinase (PI3K)/Akt/glycogen synthase kinase-3β (GSK-3β) signaling pathway. A total of 96 newborn Wistar rats aged 7 days were randomly divided into four groups: sham surgery, HI, drug prevention (PROG) and Akt inhibitor groups. HI animal models were established by a conventional method. All animals were sacrificed 24 h after hypoxia. Immunohistochemistry was used to detect the distribution and expression of phosphorylated Akt (p-Akt) and the GSK-3β proteins in the brain, and western blot analysis was used to determine the p-Akt and GSK-3β protein contents. An enzyme-linked immunosorbent assay was also used to determine the GSK-3β content of the brain tissue, and flow cytometry was used to evaluate the apoptosis rate of neural cells. The expression of p-Akt protein was reduced in the brain tissues of the HI group, whereas GSK-3β expression was increased. In addition, the GSK-3β content of the brain and the neuronal apoptosis rate were significantly increased. PROG pre-treatment increased p-Akt expression, decreased GSK-3β expression and GSK-3β content, and also reduced neuronal apoptosis. Following administration of the Akt inhibitor wortmannin, p-Akt expression decreased, GSK-3β expression increased, and the GSK-3β content and neuronal apoptosis rate significantly increased (P<0.05). In conclusion, PROG activates the PI3K/Akt/GSK-3β pathway to promote Akt activation, enhance p-Akt expression and inhibit GSK-3β expression, thereby inhibiting neuronal apoptosis, alleviating HI brain injury and inducing a cerebroprotective effect.