Wan Lishu, Sun Yingjie, Zhang Fan, Ren Yan
Department of Neurology, The First Hospital of Dandong, Baoshan Street No. 76, Yuanbao District, Dandong city, 118000, Liaoning Province, China.
Department of Medicine, The Central Hospital of Dandong, Dandong, China.
Cell Mol Neurobiol. 2016 Nov;36(8):1279-1289. doi: 10.1007/s10571-015-0325-0. Epub 2016 Jan 29.
Homocysteine (Hcy) is a non-essential amino acid that is derived from the breakdown of dietary methionine. Hyperhomocysteinemia (HHcy) is an independent risk factor for a variety of chronic diseases, especially neurodegenerative conditions. To better understand the role of HHcy in the pathogenesis of neurodegenerative disorders, we investigated the effect of Hcy on the proliferation and activation of microglia Bv2 cells. Cells were treated with six different Hcy concentrations: 0, 50, 100, 300, 500, and 1000 µM for different time periods (8, 12, 16, 24, and 48 h). The morphology of Bv2 cells was observed, and cell activity and proliferation were detected. Cell migration and secretion of pro-inflammatory cytokines were detected by the scratch wound assay, the transwell assay, and ELISA, respectively. The effect of Hcy on Bv2 proliferation occurred earlier (<24 h, especially 16 h) after treatment with concentrations between 100 and 300 μM, and there was no cytotoxicity to Bv2 cells. Meanwhile, functional assays suggested that Hcy not only promoted Bv2 secretion of the pro-inflammatory cytokines IL-1β, TNF-α, and IL-6, but also enhanced Bv2 migration and invasion, with 100 μM being the most effective concentration. In summary, Bv2 proliferation and activation can be promoted by short-term treatment with low-dose Hcy.
同型半胱氨酸(Hcy)是一种非必需氨基酸,由膳食蛋氨酸分解产生。高同型半胱氨酸血症(HHcy)是多种慢性疾病尤其是神经退行性疾病的独立危险因素。为了更好地理解HHcy在神经退行性疾病发病机制中的作用,我们研究了Hcy对小胶质细胞Bv2细胞增殖和活化的影响。用六种不同浓度的Hcy(0、50、100、300、500和1000 μM)处理细胞不同时间段(8、12、16、24和48小时)。观察Bv2细胞的形态,检测细胞活性和增殖情况。分别通过划痕试验、Transwell试验和ELISA检测细胞迁移和促炎细胞因子的分泌。在用100至300 μM浓度处理后,Hcy对Bv2增殖的影响在较早时间(<24小时,尤其是16小时)出现,且对Bv2细胞无细胞毒性。同时,功能试验表明,Hcy不仅促进Bv2分泌促炎细胞因子IL-1β、TNF-α和IL-6,还增强Bv2的迁移和侵袭能力,其中100 μM为最有效浓度。总之,低剂量Hcy短期处理可促进Bv2细胞的增殖和活化。