Neuroprotective effect of phospholipase A2 from Malaysian Naja Sumatrana venom against H2O2-induced cell damage and apoptosis

• Main Authors: Abdullah, Nur Atiqah Haizum, Sainik, Nur Qisya Afifah Veronica, Esa, Ezalia, Muhamad Hendri, Nur Afrina, Ahmad Rusmili, Muhamad Rusdi, Hodgson, Wayne C., Shaikh, Mohd Farooq, Othman, Iekhsan
• Format: Article
• Language: English; English
• Published: Frontiers Media S.A. 2022
• Subjects: RM300 Drugs and their action; RS Pharmacy and materia medica
• Online Access: http://irep.iium.edu.my/103691/3/103691_Neuroprotective%20effect%20of%20phospholipase%20A2_SCOPUS.pdf; http://irep.iium.edu.my/103691/4/103691_Neuroprotective%20effect%20of%20phospholipase%20A2.pdf; http://irep.iium.edu.my/103691/; https://www.frontiersin.org/articles/10.3389/fphar.2022.935418/pdf; https://doi.org/10.3389/fphar.2022.935418
• Institution: Universiti Islam Antarabangsa Malaysia

Oxidative stress is one of the factors involved in the pathogenesis of several neurodegenerative diseases. It has been reported that a secretory phospholipase A2 known as A2-EPTX-NSm1a has lower cytotoxicity in neuronal cells compared to its crude Naja sumatrana venom. In this study, A2-EPTX-NSm1a was tested for its neuroprotective activity on human neuroblastoma cells (SH-SY5Y) differentiated into cholinergic neurons against oxidative stress induced by hydrogen peroxide (H2O2). H2O2 treatment alone increased the caspase-3 and caspase-8 activities, whereas pre-treatment with A2-EPTX-NSm1a reduced the activity of these apoptosis-associated proteins. Moreover, A2-EPTX-NSm1a protects the morphology and ultrastructure of differentiated SH-SY5Y cells in the presence of H2O2. Oxidative stress increased the number of small mitochondria. Further evaluation showed the size of mitochondria with a length below 0.25 µm in oxidative stress conditions is higher than the control group, suggesting mitochondria fragmentation. Pre-treatment with A2-EPTX-NSm1a attenuated the number of mitochondria in cells with H2O2 Furthermore, A2-EPTX-NSm1a altered the expression of several neuroprotein biomarkers of GDNF, IL-8, MCP-1, TIMP-1, and TNF-R1 in cells under oxidative stress induced by H2O2. These findings indicate that anti-apoptosis with mitochondria-related protection, anti-inflammatory effect, and promote expression of important markers for cell survival may underlie the neuroprotective effect of A2-EPTX-NSm1a in cholinergic rich human cells under oxidative stress, a vital role in the neuronal disorder.