叶酸和合成生物活性化合物单独及联合作用对人小胶质细胞中 Abeta(25-35)诱导毒性的影响。

The isolated and combined effects of folic acid and synthetic bioactive compounds against Abeta(25-35)-induced toxicity in human microglial cells.

机构信息

Department of Nutritional Science, Fu-Jen University, 510 Chung-Cheng Rd., Hsinchuang, Taipei County 242, Taiwan.

出版信息

Molecules. 2010 Mar 11;15(3):1632-44. doi: 10.3390/molecules15031632.

DOI:10.3390/molecules15031632

PMID:20336004

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6257320/

Abstract

Folic acid plays an important role in neuronal development. A series of newly synthesized bioactive compounds (NSCs) was reported to exhibit immunoactive and neuroprotective functions. The isolated and combined effects of folic acid and NSCs against beta-amyloid (Abeta)-induced cytotoxicity are poorly understood. These effects were tested using human microglia cells (C13NJ) subjected to Abeta(25-35) challenge. According to an MTT assay, treatment of C13NJ cells with Abeta(25-35) at 10-100 microM for 48 h induced 18%-43% cellular death in a dose-dependent manner (p < 0.05). Abeta(25-35) treatment at 25 microM induced nitrite oxide (NO) release, elevated superoxide production, and reduced the distribution of cells in the S phase. Preincubation of C13NJ with 100 microM folic acid protected against Abeta(25-35)-induced cell death, which coincided with a reduction in NO release by folic acid supplements. NSC47 at a level of 50 microM protected against Abeta(25-35)-induced cell death and reduced Abeta-promoted superoxide production (p < 0.05). Folic acid in combination with NSC47 at their cytoprotective doses did not synergistically ameliorate Abeta(25-35)-associated NO release, superoxide production, or cell cycle arrest. Taken together, folic acid or NSC treatment alone, but not the combined regimen, protected against Abeta(25-35)-induced cell death, which may partially, if not completely, be mediated by free radical-scavenging effects.

摘要

叶酸在神经元发育中起着重要作用。一系列新合成的生物活性化合物（NSC）被报道具有免疫活性和神经保护功能。叶酸和 NSC 对β-淀粉样蛋白（Abeta）诱导的细胞毒性的单独和联合作用知之甚少。使用β淀粉样蛋白（Abeta）（25-35）挑战的人小神经胶质细胞（C13NJ）测试这些作用。根据 MTT 测定，用 10-100μM 的 Abeta（25-35）处理 C13NJ 细胞 48 小时以剂量依赖性方式诱导 18％-43％的细胞死亡（p<0.05）。用 25μM 的 Abeta（25-35）处理诱导亚硝酸盐氧化（NO）释放，增加超氧化物产生，并减少细胞在 S 期的分布。用 100μM 叶酸预先孵育 C13NJ 可防止 Abeta（25-35）诱导的细胞死亡，这与叶酸补充剂减少 NO 释放一致。50μM 的 NSC47 可防止 Abeta（25-35）诱导的细胞死亡，并减少 Abeta 促进的超氧化物产生（p<0.05）。叶酸与 NSC47 在其细胞保护剂量下联合使用不会协同改善 Abeta（25-35）相关的 NO 释放，超氧化物产生或细胞周期停滞。总之，叶酸或 NSC 单独治疗，而不是联合治疗，可防止 Abeta（25-35）诱导的细胞死亡，这可能部分（如果不是完全）通过清除自由基的作用介导。