Departamento de Farmacologia, Instituto de Ciências Biomédicas, Universidade of São Paulo, São Paulo, SP, Brasil.
Braz J Med Biol Res. 2012 Jan;45(1):58-67. doi: 10.1590/s0100-879x2011007500157. Epub 2011 Nov 25.
Wnt proteins are involved in tissue development and their signaling pathways play an important role during embryogenesis. Wnt signaling can promote cell survival, which is beneficial for neurons, but could also lead to tumor development in different tissues. The present study investigated the effects of a Wnt protein on the susceptibility of a neural tumor cell line (PC12 cells) to the cytotoxic compounds ferrous sulfate (10 mM), staurosporine (100 and 500 nM), 3-nitropropionic acid (5 mM), and amyloid β-peptide (Aβ25-35; 50 µM). Cells (1 x 10(6) cells/mL) were treated with the Wnt-3a recombinant peptide (200 ng/mL) for 24 h before exposure to toxic insults. The Wnt-3a protein partially protected PC12 cells, with a 6-15% increase in cell viability in the presence of toxic agents, similar to the effect measured using the MTT and lactate dehydrogenase cell viability assays. The Wnt-3a protein increased protein expression of β-catenin by 52% compared to control. These findings suggest that Wnt signaling can protect neural cells against apoptosis induced by toxic agents, which are relevant to the pathogenesis of Alzheimer's and Huntington's diseases.
Wnt 蛋白参与组织发育，其信号通路在胚胎发生过程中发挥着重要作用。Wnt 信号可以促进细胞存活，这对神经元有益，但也可能导致不同组织中的肿瘤发展。本研究探讨了一种 Wnt 蛋白对神经肿瘤细胞系（PC12 细胞）对铁硫酸（10 mM）、星形孢菌素（100 和 500 nM）、3-硝基丙酸（5 mM）和淀粉样 β 肽（Aβ25-35；50 µM）等细胞毒性化合物敏感性的影响。细胞（1 x 10(6)个细胞/毫升）在暴露于有毒物质之前用 Wnt-3a 重组肽（200 ng/mL）处理 24 小时。Wnt-3a 蛋白部分保护 PC12 细胞，在有毒物质存在时细胞活力增加 6-15%，与 MTT 和乳酸脱氢酶细胞活力测定测量的效果相似。Wnt-3a 蛋白使 β-连环蛋白的蛋白表达增加了 52%，与对照组相比。这些发现表明，Wnt 信号可以保护神经细胞免受毒性物质诱导的细胞凋亡，这与阿尔茨海默病和亨廷顿病的发病机制有关。
