Neuroprotective Effects of Activated Protein C Involve the PARP/AIF Pathway against Oxygen-Glucose Deprivation in SH-SY5Y Cells
Protein C, a member of the zymogen family of serine proteases in plasma, is one of the several vitamin K dependent glycoproteins known to induce anti-apoptotic activity. However, the target molecule involved in the mechanism needs to be investigated. We sought to investigate the pathways involved in...
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MDPI AG
2020-12-01
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| author | Mukesh Kumar Sriwastva Remesh Kunjunni Mutahar Andrabi Kameshwar Prasad Renu Saxena Vivekanandhan Subbiah |
| author_facet | Mukesh Kumar Sriwastva Remesh Kunjunni Mutahar Andrabi Kameshwar Prasad Renu Saxena Vivekanandhan Subbiah |
| author_sort | Mukesh Kumar Sriwastva |
| collection | DOAJ |
| description | Protein C, a member of the zymogen family of serine proteases in plasma, is one of the several vitamin K dependent glycoproteins known to induce anti-apoptotic activity. However, the target molecule involved in the mechanism needs to be investigated. We sought to investigate the pathways involved in the anti-apoptotic role of activated protein C (APC) on oxygen-glucose deprivation (OGD) induced ischemic conditions in in-vitro SH-SY5Y cells. SH-SY5Y cells were exposed to OGD in an airtight chamber containing 95% N<sub>2</sub> and 5% CO<sub>2</sub> and media deprived of glucose for 4 h following 24 h of reoxygenation. The cell toxicity, viability, expression of receptors such as endothelial cell protein C receptor (EPCR), protease-activated receptor (PAR)1, PAR3, and apoptosis-related proteins B-cell lymphoma 2 (BCL-2), BCL-2-like protein 4 (Bax), Poly [ADP-ribose] polymerase-1 (PARP-1) were assessed. Administration of APC decreased the cellular injury when compared to the OGD exposed group in a dose-dependent manner and displayed increased expression of PAR-1, PAR-3, and EPCR. The APC treatment leads to a reduction in PARP-1 expression and cleavage and apoptosis-inducing factor (AIF) expression. The reduction of caspase-3 activity and PARP-1 and AIF expression following APC administration results in restoring mitochondrial function with decreased cellular injury and apoptosis. Our results suggested that APC has potent protective effects against in-vitro ischemia in SH-SY5Y cells by modulating mitochondrial function. |
| first_indexed | 2024-03-10T14:11:43Z |
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| language | English |
| last_indexed | 2024-03-10T14:11:43Z |
| publishDate | 2020-12-01 |
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| series | Brain Sciences |
| spelling | doaj.art-6e45fe2ad2c64da4938ef982292af1902023-11-21T00:06:43ZengMDPI AGBrain Sciences2076-34252020-12-01101295910.3390/brainsci10120959Neuroprotective Effects of Activated Protein C Involve the PARP/AIF Pathway against Oxygen-Glucose Deprivation in SH-SY5Y CellsMukesh Kumar Sriwastva0Remesh Kunjunni1Mutahar Andrabi2Kameshwar Prasad3Renu Saxena4Vivekanandhan Subbiah5Department of Neurobiochemistry, All India Institute of Medical Sciences, New Delhi 110029, IndiaDepartment of Neurobiochemistry, All India Institute of Medical Sciences, New Delhi 110029, IndiaDepartment of Neurobiochemistry, All India Institute of Medical Sciences, New Delhi 110029, IndiaDepartment of Neurology, All India Institute of Medical Sciences, New Delhi 110029, IndiaDepartment of Hematology, All India Institute of Medical Sciences, New Delhi 110029, IndiaDepartment of Neurobiochemistry, All India Institute of Medical Sciences, New Delhi 110029, IndiaProtein C, a member of the zymogen family of serine proteases in plasma, is one of the several vitamin K dependent glycoproteins known to induce anti-apoptotic activity. However, the target molecule involved in the mechanism needs to be investigated. We sought to investigate the pathways involved in the anti-apoptotic role of activated protein C (APC) on oxygen-glucose deprivation (OGD) induced ischemic conditions in in-vitro SH-SY5Y cells. SH-SY5Y cells were exposed to OGD in an airtight chamber containing 95% N<sub>2</sub> and 5% CO<sub>2</sub> and media deprived of glucose for 4 h following 24 h of reoxygenation. The cell toxicity, viability, expression of receptors such as endothelial cell protein C receptor (EPCR), protease-activated receptor (PAR)1, PAR3, and apoptosis-related proteins B-cell lymphoma 2 (BCL-2), BCL-2-like protein 4 (Bax), Poly [ADP-ribose] polymerase-1 (PARP-1) were assessed. Administration of APC decreased the cellular injury when compared to the OGD exposed group in a dose-dependent manner and displayed increased expression of PAR-1, PAR-3, and EPCR. The APC treatment leads to a reduction in PARP-1 expression and cleavage and apoptosis-inducing factor (AIF) expression. The reduction of caspase-3 activity and PARP-1 and AIF expression following APC administration results in restoring mitochondrial function with decreased cellular injury and apoptosis. Our results suggested that APC has potent protective effects against in-vitro ischemia in SH-SY5Y cells by modulating mitochondrial function.https://www.mdpi.com/2076-3425/10/12/959neuroprotectionactivated protein Ccerebral ischemiaoxygen-glucose deprivation |
| spellingShingle | Mukesh Kumar Sriwastva Remesh Kunjunni Mutahar Andrabi Kameshwar Prasad Renu Saxena Vivekanandhan Subbiah Neuroprotective Effects of Activated Protein C Involve the PARP/AIF Pathway against Oxygen-Glucose Deprivation in SH-SY5Y Cells Brain Sciences neuroprotection activated protein C cerebral ischemia oxygen-glucose deprivation |
| title | Neuroprotective Effects of Activated Protein C Involve the PARP/AIF Pathway against Oxygen-Glucose Deprivation in SH-SY5Y Cells |
| title_full | Neuroprotective Effects of Activated Protein C Involve the PARP/AIF Pathway against Oxygen-Glucose Deprivation in SH-SY5Y Cells |
| title_fullStr | Neuroprotective Effects of Activated Protein C Involve the PARP/AIF Pathway against Oxygen-Glucose Deprivation in SH-SY5Y Cells |
| title_full_unstemmed | Neuroprotective Effects of Activated Protein C Involve the PARP/AIF Pathway against Oxygen-Glucose Deprivation in SH-SY5Y Cells |
| title_short | Neuroprotective Effects of Activated Protein C Involve the PARP/AIF Pathway against Oxygen-Glucose Deprivation in SH-SY5Y Cells |
| title_sort | neuroprotective effects of activated protein c involve the parp aif pathway against oxygen glucose deprivation in sh sy5y cells |
| topic | neuroprotection activated protein C cerebral ischemia oxygen-glucose deprivation |
| url | https://www.mdpi.com/2076-3425/10/12/959 |
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