|
|
|
| Oligodendrocytes-like conditional medium can improve oxidative stress damage of SH-SY5Y cells by regulating Sirt1/PGC-α pathway#br# |
| NIU Dongdong1, LING Yating1, LYU Xiaorui1, WANG Ziyu2, HU Jiabo1 |
(1. School of Medicine, Jiangsu University, Zhenjiang Jiangsu 212013; 2. Health Clinical Laboratories, Health BioMed Co. Ltd., Ningbo Zhejiang 315042, China)
|
|
|
|
Abstract Objective： To explore the repair effect of oligodendrocyteslike conditioned medium (OCM) derived from human neural stem cells (hNSCs) on human neuron and its possible mechanism. Methods： Human neural stem cells differentiated into oligodendrocytes-like (OLs), which were identified by immunofluorescence and their myelination ability was observed in vitro. The oxidative damage model of SH-SY5Y cells was induced by H2O2. Reactive oxygen species (ROS) and cell apoptosis were determined by flow cytometry. Mitochondrial membrane potential was detected by fluorescence microscopy. SOD, GSH and MDA were detected by chemiluminescence. The protein level of Sirt1/PGC-1α was determined by Western blotting. Results： Human neural stem cellderived oligodendrocytes-like (hNSC-OLs) have a typical oligodendrocyte morphology and express oligodendrocyte markers Olig2 and SOX10, the formation of myelin sheath around axons was observed in vitro. OCM significantly increased the vitality of the damaged cells (P<0.01), decreased ROS level (P<0.01), increased mitochondrial membrane potential, increased GSH, SOD level (P<0.01), decreased MDA content (P<0.01), and decreased apoptosis level (P<0.01). OCM treatment increased the expression levels of Sirt1 and PGC-1α protein (P<0.05), and was specifically inhibited by the inhibitor EX527 (P<0.05). Conclusion： hNSC-OLs have myelination ability in vitro, and its conditioned medium can improve H2O2induced oxidative stress of SH-SY5Y cells and reduce SHSY5Y cell apoptosis through Sirt1/PGC-1α pathway.
|
|
Received: 18 February 2023
|
|
|
|
［1］Biswas S, Chung SH, Jiang P, et al. Development of glial restricted human neural stem cells for oligodendrocyte differentiation in vitro and in vivo［J］. Sci Rep, 2019, 9(1): 9013.
［2］宋聖姣, 李娟, 吴文成, 等. 少突胶质细胞的功能与脱髓鞘疾病［J］. 中国组织工程研究, 2021, 26(19): 3108-3116.
［3］Luo JXX, Cui Q, Yaqubi M, et al. Human oligodendrocyte myelination potential; Relation to age and differentiation［J］. Ann Neurol, 2022, 91(2): 178-191.
［4］Xu L, Zhang M, Shi L, et al. Neural stemness contributes to cell tumorigenicity［J］. Cell Biosci, 2021, 11(1): 21.
［5］Kumar RR, Singh L, Thakur A, et al. Role of vitamins in neurodegenerative diseases: A review［J］. CNS Neurol Disord Drug Targets, 2022, 21(9): 766-773.
［6］Chen X, Ye K, Yu J, et al. Regeneration of sciatic nerves by transplanted microvesicles of human neural stem cells derived from embryonic stem cells［J］. Cell Tissue Bank, 2020, 21(2): 233-248.
［7］Asefy Z, Khusro A, Mammadova S, et al. Melatonin hormone as a therapeutic weapon against neurodegenerative diseases［J］. Cell Mol Biol (Noisylegrand), 2021, 67(3): 99-106.
［8］Radermacher KA, Wingler K, Langhauser F, et al. Neuroprotection after stroke by targeting NOX4 as a source of oxidative stress［J］. Antioxid Redox Signal, 2013, 18(12): 1418-1427.
［9］Li H, Tang Z, Chu P, et al. Neuroprotective effect of phosphocreatine on oxidative stress and mitochondrial dysfunction induced apoptosis in vitro and in vivo: Involvement of dual PI3K/Akt and Nrf2/HO1 pathways［J］. Free Radic Biol Med, 2018, 120: 228-238.
［10］余佳红, 童玉, 叶开, 等. 人神经干细胞微囊泡对谷氨酸诱导PC12细胞损伤的保护作用［J］. 江苏大学学报（医学版）, 2020, 30(4): 302-306.
［11］叶开, 余佳红, 陈天琰, 等. 人神经干细胞源施万样细胞微囊泡促进大鼠神经元轴突生长［J］. 江苏大学学报（医学版）, 2019, 29(4): 326-332.
［12］钟欣, 栾佐, 臧静, 等. 人少突胶质前体细胞移植对脑白质损伤大鼠的保护作用［J］. 中国当代儿科杂志, 2021, 23(4): 410-415.
［13］Doseděl M, Jirkovsky＇ E, Mackov K, et al. Vitamin Csources, physiological role, kinetics, deficiency, use, toxicity, and determination［J］. Nutrients, 2021, 13(2): 615.
［14］王丹, 吕懿, 曹彬, 等. 维生素E, 维生素C, 牛磺酸对苯并［a］芘致SHSY5Y细胞能量代谢损伤的影响［J］. 环境与职业医学, 2019, 36(2): 181-185.
［15］Ni W, Zhou J, Ling Y, et al. Neural stem cell secretome exerts a protective effect on damaged neuron mitochondria in Parkinson′s disease model［J］. Brain Res, 2022, 1790: 147978.
［16］Kong S, Cai B, Nie Q. PGC1α affects skeletal muscle and adipose tissue development by regulating mitochondrial biogenesis［J］. Mol Genet Genomics, 2022, 297(3): 621-633.
［17］Zhu Y, Zhu X, Zhou Y, et al. Reduced serum SIRT1 levels in patients with Parkinson′s disease: a crosssectional study in China［J］. Neurol Sci, 2021, 42(5): 1835-1841.
［18］Tan F, Dong W, Lei X, et al. Attenuated SUMOylation of sirtuin 1 in premature neonates with bronchopulmonary dysplasia［J］. Mol Med Rep, 2018, 17(1): 1283-1288.
［19］Huang Q, Su H, Qi B, et al. A SIRT1 activator, ginsenoside Rc, promotes energy metabolism in cardiomyocytes and neurons［J］. J Am Chem Soc, 2021, 143(3): 1416-1427.
［20］Long H, Cheng Y, Zhou Z, et al. The key roles of organelles and ferroptosis in Alzheimer′s disease［J］. J Neurosci Res, 2022, 100(6): 1257-1280. |
| [1] |
. [J]. Journal of Jiangsu University(Medicine Edition), 2023, 33(04): 364-368. |
|
|
|
|
