Activation of AKT1/GSK-3β/β-Catenin–TRIM11/Survivin Pathway by Novel GSK-3β Inhibitor Promotes Neuron Cell Survival: Study in Differentiated SH-SY5Y Cells in OGD Model
| العنوان: | Activation of AKT1/GSK-3β/β-Catenin–TRIM11/Survivin Pathway by Novel GSK-3β Inhibitor Promotes Neuron Cell Survival: Study in Differentiated SH-SY5Y Cells in OGD Model |
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| المؤلفون: | M. Ramanathan, B. S. Darshit |
| المصدر: | Molecular Neurobiology. 53:6716-6729 |
| بيانات النشر: | Springer Science and Business Media LLC, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | 0301 basic medicine, Time Factors, SH-SY5Y, Cell Survival, Survivin, Ubiquitin-Protein Ligases, Cellular differentiation, Neuroscience (miscellaneous), Retinoic acid, Down-Regulation, Apoptosis, Caspase 3, Biology, Models, Biological, Inhibitor of Apoptosis Proteins, Tripartite Motif Proteins, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, 0302 clinical medicine, Cell Line, Tumor, Humans, Protein Kinase Inhibitors, GSK3B, beta Catenin, Neurons, Glycogen Synthase Kinase 3 beta, L-Lactate Dehydrogenase, Cell Differentiation, Molecular biology, Neuroprotection, Up-Regulation, Cell biology, Gene Expression Regulation, Neoplastic, Oxygen, Glucose, 030104 developmental biology, Neurology, chemistry, Catenin, Signal transduction, Proto-Oncogene Proteins c-akt, Biomarkers, 030217 neurology & neurosurgery, Signal Transduction |
| الوصف: | The objective of this study is to elucidate the effect of a new glycogen synthase kinase-3β (GSK-3β) inhibitor in RA differentiated SH-SY5Y cells in oxygen and glucose deprivation (OGD) model. The pathway involved in GSK-3β signaling during OGD was measured to elucidate the mechanism of action. The differentiation of SH-SY5Y into mature neuronal cells was done with retinoic acid. During differentiation, upregulation of the growth-associated protein 43 (GAP43), neurogenin1 (NGN1), neuronal differentiation 2 (NeuroD2), and tripartite motif containing 11 (TRIM11) genes were observed. Twelve hours of optimal OGD exposure resulted in the alteration of GSK-3β functions of the neuron cells. Of the five molecules selected for this study, molecule G3 showed better effect in the initial phase of the study. Hence, G3 (0.5, 1, and 5 μM) was selected for further study in the OGD model. The standard GSK-3β inhibitor, AR-A014418 (1 μM), was used for comparison. Molecules were pretreated (30 min) and cotreated during OGD exposure. GSK-3β inhibitors showed antiapoptotic activity as evidenced by reduced caspase-3 enzyme activity and increased survivin transcription, as well as improved membrane integrity, evidenced by LDH assay. The inhibitor molecules also up-regulated survival AKT1/GSK-3β/β-catenin pathway and stabilized β-catenin. Inhibition of GSK-3β maintained neuronal survival by upregulating GAP43, Ngn1, and NeuroD2 gene transcription. Further GSK-3β inhibition reduced the TRIM11 gene transcription. In conclusion, both inhibitors have been found to control apoptosis and maintain neuronal functioning and this effect might have been mediated through AKT1/GSK-3β/β-catenin-TRIM11/survivin pathway. |
| تدمد: | 1559-1182 0893-7648 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::52a147193ff5fbe0a61637afd73ec2a9Test https://doi.org/10.1007/s12035-015-9598-zTest |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....52a147193ff5fbe0a61637afd73ec2a9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15591182 08937648 |
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