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Neuroprotective Effects of Activated Protein C Involve the PARP/AIF Pathway against Oxygen-Glucose Deprivation in SH-SY5Y Cells

1
Department of Neurobiochemistry, All India Institute of Medical Sciences, New Delhi 110029, India
2
Department of Neurology, All India Institute of Medical Sciences, New Delhi 110029, India
3
Department of Hematology, All India Institute of Medical Sciences, New Delhi 110029, India
*
Author to whom correspondence should be addressed.
Brain Sci. 2020, 10(12), 959; https://doi.org/10.3390/brainsci10120959
Received: 10 November 2020 / Revised: 3 December 2020 / Accepted: 7 December 2020 / Published: 10 December 2020
(This article belongs to the Section Molecular and Cellular Neuroscience)
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% N2 and 5% CO2 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. View Full-Text
Keywords: neuroprotection; activated protein C; cerebral ischemia; oxygen-glucose deprivation neuroprotection; activated protein C; cerebral ischemia; oxygen-glucose deprivation
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MDPI and ACS Style

Sriwastva, M.K.; Kunjunni, R.; Andrabi, M.; Prasad, K.; Saxena, R.; Subbiah, V. Neuroprotective Effects of Activated Protein C Involve the PARP/AIF Pathway against Oxygen-Glucose Deprivation in SH-SY5Y Cells. Brain Sci. 2020, 10, 959. https://doi.org/10.3390/brainsci10120959

AMA Style

Sriwastva MK, Kunjunni R, Andrabi M, Prasad K, Saxena R, Subbiah V. Neuroprotective Effects of Activated Protein C Involve the PARP/AIF Pathway against Oxygen-Glucose Deprivation in SH-SY5Y Cells. Brain Sciences. 2020; 10(12):959. https://doi.org/10.3390/brainsci10120959

Chicago/Turabian Style

Sriwastva, Mukesh K., Remesh Kunjunni, Mutahar Andrabi, Kameshwar Prasad, Renu Saxena, and Vivekanandhan Subbiah. 2020. "Neuroprotective Effects of Activated Protein C Involve the PARP/AIF Pathway against Oxygen-Glucose Deprivation in SH-SY5Y Cells" Brain Sciences 10, no. 12: 959. https://doi.org/10.3390/brainsci10120959

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