Inhibition on Apoptosis Induced by Elevated Hydrostatic Pressure in Retinal Ganglion Cell-5 via Laminin Upregulating β1-integrin/Focal Adhesion Kinase/Protein Kinase B Signaling Pathway
| Autor: | Yan-Ming Chen, Ming-Ming Sun, Xiao-Dan Guo, Ya-Chen Wang, Yi Li, Zhong-zhi Zhang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Retinal Ganglion Cells genetic structures Hydrostatic pressure lcsh:Medicine Apoptosis Biology Retinal ganglion 03 medical and health sciences 0302 clinical medicine Annexin medicine Hydrostatic Pressure Humans Protein kinase B PI3K/AKT/mTOR pathway Cells Cultured Intraocular Pressure Akt/PKB signaling pathway Integrin beta1 lcsh:R Glaucoma Laminin General Medicine eye diseases Cell biology Up-Regulation 030104 developmental biology medicine.anatomical_structure Retinal ganglion cell Protein kinase B signaling Focal Adhesion Protein-Tyrosine Kinases Immunology Original Article sense organs Proto-Oncogene Proteins c-akt 030217 neurology & neurosurgery |
| Zdroj: | Chinese Medical Journal Chinese Medical Journal, Vol 129, Iss 8, Pp 976-983 (2016) |
| ISSN: | 0366-6999 |
| Popis: | Background: Glaucoma is a progressive optic neuropathy characterized by degeneration of neurons due to loss of retinal ganglion cells (RGCs). High intraocular pressure (HIOP), the main risk factor, causes the optic nerve damage. However, the precise mechanism of HIOP-induced RGC death is not yet completely understood. This study was conducted to determine apoptosis of RGC-5 cells induced by elevated hydrostatic pressures, explore whether laminin is associated with apoptosis under pressure, whether laminin can protect RGCs from apoptosis and affirm the mechanism that regulates the process of RGCs survival. Methods: RGC-5 cells were exposed to 0, 20, 40, and 60 mmHg in a pressurized incubator for 6, 12, and 24 h, respectively. The effect of elevated hydrostatic pressure on RGC-5 cells was measured by Annexin V-fluorescein isothiocyanate/propidium iodide staining, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and Western blotting of cleaved caspase-3 protein. Location and expression of laminin were detected by immunofluorescence. The expression of β1-integrin, phosphorylation of focal adhesion kinase (FAK) and protein kinase B (PKB, or AKT) were investigated with real-time polymerase chain reaction and Western blotting analysis. Results: Elevated hydrostatic pressure induced apoptosis in cultured RGC-5 cells. Pressure with 40 mmHg for 24 h induced a maximum apoptosis. Laminin was declined in RGC-5 cells after exposing to 40 mmHg for 24 h. After pretreating with laminin, RGC-5 cells survived from elevated pressure. Furthermore, β1-integrin and phosphorylation of FAK and AKT were increased compared to 40 mmHg group. Conclusions: The data show apoptosis tendency of RGC-5 cells with elevated hydrostatic pressure. Laminin can protect RGC-5 cells against high pressure via β1-integrin/FAK/AKT signaling pathway. These results suggest that the decreased laminin of RGC-5 cells might be responsible for apoptosis induced by elevated hydrostatic pressure, and laminin or activating β1-integrin/FAK/AKT pathway might be potential treatments to prevent RGC loss in glaucomatous optic neuropathy. |
| Databáze: | OpenAIRE |
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