Expression of Bcl-2 and Bad in hippocampus of status epileptic rats and molecular mechanism of intervened recombinant human erythropoietin
Authors:
Open Access
- 5 June 2018
- journal article
- research article
- Published by Spandidos Publications in Experimental and Therapeutic Medicine
- Vol. 16 (2) , 847-855
Abstract
Injury of hippocampal neurons in status epilepticus (SE) SD rats kindled by pentylenetetrazol (PTZ) were studied, and the changes of apoptosis neurons, protein expression of Bad and Bcl-2 alone and combined application of phosphatidyl inositol 3-kinase (PI3K) inhibitor LY294002 and recombinant human erythropoietin (rHuEpo) were evaluated for the possible mechanisms of rHuEpo. The SE rats kindled by the PTZ were randomly divided into normal control group [normal saline (NS)], model group (PTZ + NS), rHuEpo treated group (PTZ + rHuEpo), LY294002 treated group (PTZ + LY294002 + rHuEpo) and LY294002 control group (rHuEpo + PTZ + DMSO). Apoptosis of hippocampal neurons was detected by TUNEL method; expression of phosphorylation protein kinase B (p-PKB/p-Akt), Bcl-2 and Bad were detected by immunohistochemistry; the expression of Bcl-2 mRNA, Bad mRNA in hippocampal neurons of rats were detected through reverse transcription polymerase chain reaction (RT-PCR); the expression of Akt, p-Akt and Bcl-2, Bad protein in hippocampal neurons of rats were detected by western blotting. The amount of apoptotic neurons was less in the rHuEpo treated group and the LY294002 control group than in the LY294002 treated group (P<0.05). The expression of p-Akt protein and Bcl-2 protein increased while the Bad protein decreased significantly in the rHuEpo treated group and the LY294002 control group compared with the LY294002 treated group (P<0.05). The expression of Bad protein and Bad mRNA in hippocampus increased while the p-Akt, Bcl-2, Bcl-2 mRNA decreased significantly in the LY294002 treated group compared with the rHuEpo treated group (P<0.05). The PI3K/Akt signaling pathway is one of the pathways of rHuEpo neuroprotective effects and was confirmed from both the of positive and negative aspects. rHuEpo regulates the expression of mitochondrial apoptotic pathway related factors Bad and Bcl-2 to inhibit apoptosis and promotes neuronal survival.Keywords
This publication has 19 references indexed in Scilit:
- The Calcineurin Inhibitor FK506 Prevents Cognitive Impairment by Inhibiting Reactive Astrogliosis in Pilocarpine-Induced Status Epilepticus RatsFrontiers in Cellular Neuroscience, 2018
- Erythropoietin ameliorates diabetes-associated cognitive dysfunction in vitro and in vivoScientific Reports, 2017
- Neuroprotective effects of ginseng protein on PI3K/Akt signaling pathway in the hippocampus of D -galactose/AlCl 3 inducing rats model of Alzheimer’s diseaseJournal of Ethnopharmacology, 2016
- Role of the Mitochondrial Calcium Uniporter in Rat Hippocampal Neuronal Death After Pilocarpine-Induced Status EpilepticusNeurochemical Research, 2015
- The Effect of Recombinant Erythropoietin on Plasma Brain Derived Neurotrophic Factor Levels in Patients with Affective Disorders: A Randomised Controlled StudyPLOS ONE, 2015
- Interleukin-1β plays a role in the pathogenesis of mesial temporal lobe epilepsy through the PI3K/Akt/mTOR signaling pathway in hippocampal neuronsJournal of Neuroimmunology, 2015
- Erythropoietin pretreatment suppresses seizures and prevents the increase in inflammatory mediators during pentylenetetrazole-induced generalized seizuresInternational Journal of Neuroscience, 2014
- Effects of Nicorandil in Neuroprotective Activation of PI3K/AKT Pathways in a Cellular Model of Alzheimer's DiseaseEuropean Neurology, 2013
- Protection by silibinin against experimental ischemic stroke: Up-regulated pAkt, pmTOR, HIF-1α and Bcl-2, down-regulated Bax, NF-κB expressionNeuroscience Letters, 2012
- Erythropoietin prevents the increase in blood–brain barrier permeability during pentylentetrazol induced seizuresLife Sciences, 2006