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
Neuropharmacology Research Laboratory, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia.
Faculty of Medicine, Centre for Tissue Engineering and Regenerative Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Front Pharmacol. 2022 Oct 14;13:935418. doi: 10.3389/fphar.2022.935418. eCollection 2022.
Oxidative stress is one of the factors involved in the pathogenesis of several neurodegenerative diseases. It has been reported that a secretory phospholipase A known as A2-EPTX-NSm1a has lower cytotoxicity in neuronal cells compared to its crude 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 (HO). HO 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 HO. 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 HO 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 HO. 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.
氧化应激是几种神经退行性疾病发病机制中的因素之一。据报道，一种名为A2-EPTX-NSm1a的分泌型磷脂酶A与其粗毒液相比，在神经元细胞中的细胞毒性较低。在本研究中，测试了A2-EPTX-NSm1a对分化为胆碱能神经元的人神经母细胞瘤细胞（SH-SY5Y）抵抗过氧化氢（HO）诱导的氧化应激的神经保护活性。单独的HO处理增加了caspase-3和caspase-8的活性，而用A2-EPTX-NSm1a预处理降低了这些凋亡相关蛋白的活性。此外，A2-EPTX-NSm1a在HO存在的情况下保护分化的SH-SY5Y细胞的形态和超微结构。氧化应激增加了小线粒体的数量。进一步评估表明，在氧化应激条件下，长度低于0.25μm的线粒体大小高于对照组，提示线粒体碎片化。用A2-EPTX-NSm1a预处理可减少HO处理细胞中的线粒体数量。此外，A2-EPTX-NSm1a改变了HO诱导的氧化应激条件下细胞中几种神经蛋白生物标志物GDNF、IL-8、MCP-1、TIMP-1和TNF-R1的表达。这些发现表明，具有线粒体相关保护的抗凋亡、抗炎作用以及促进细胞存活重要标志物的表达可能是A2-EPTX-NSm1a在氧化应激下对富含胆碱能的人类细胞具有神经保护作用的基础，这在神经元疾病中起着至关重要的作用。
