ALUMINUM, NEUROTOXICITY AND GENE EXPRESSION

铝被认为可能是阿尔茨海默氏症的病因 鉴于发现高浓度铝的事实而引发的疾病 受阿尔茨海默氏症神经原纤维缠结影响的神经元。 此外，兔脑脊髓内注射铝 液体诱导神经细丝在核周和细胞内积聚 流程。我们已经进行了初步的实验，并表明 氯化铝在体外降解裸DNA。建议进行实验，以 确定转录基因是否比 铝对非转录基因的损伤。由于铝离子进入 培养的细胞，我们将检测铝对不同水平的影响 使用ras癌基因在体内表达的基因表达 人神经母细胞瘤细胞系SK-N-SH。这些结果将与 这些结果是使用β-干扰素基因获得的，这种基因是一种 细胞系中的非转录基因。此外，铝的影响 在SV40不同区域的微染色体将被确定。400个BP 跨越复制起点的区域缺少组蛋白。我们会 检查这一400个碱基点的区域是否比 微染色体的其他部分。铝对ras基因表达的影响 而对SK-N-SH细胞中ras蛋白的合成也将 下定决心。最后，铝对基因表达的影响。 质粒编码的G418抗生素耐药基因将被引入 采用DNA转染法对SK-N-SH细胞进行鉴定。这些 结果应该表明基因是否表现出对 铝的损伤，以及组蛋白是否可能参与了 保护DNA免受铝的伤害。在任何一种情况下，基金会都将是 为进一步研究退行性变中的铝毒性而建立 疾病。

Aluminum has been implicated as a possible etiological agent in Alzheimer's disease in view of the fact that high concentrations of aluminum are found in neurons affected with the Alzheimer's neurofibrillary tangles. Furthermore, the injection of aluminum into the rabbit cerebral spinal fluid induces accumulation of neurofilaments in the perikaryon and cell processes. We have performed preliminary experiments and have shown that aluminum chloride degrades naked DNA in vitro. Experiments are proposed to determine whether transcribing genes are more sensitive than non-transcribing genes to damage by aluminum. Since aluminum ions enter cultured cells, we will examine the effect of aluminum on different levels of gene expression in vivo using the ras oncogene which is expressed in the human neuroblastoma cell line SK-N-SH. These results will be compared to those results obtained using the beta-interferon gene which is a nontranscribing gene in the cell line. In addition, the effect of aluminum on different regions of SV40 minichromosome will be ascertained. A 400 bp region spanning the replication origin is devoid of histones. We will examine whether this 400 bp region is more susceptible to aluminum than other portions of the minichromosome. The effect of aluminum on ras mRNA and on the synthesis of the ras protein in SK-N-SH cells will also be determined. Finally, the effect of aluminum on the expression of the plasmid-coded G418 antibiotic resistance gene which will be introduced into SK-N-SH cells by DNA transfection technique will be determined. These results should indicate whether genes show a differential sensitivity to damage by aluminum, and whether histones might be involved in the protection of DNA from aluminum. In either case, a foundation would be established for further studies of aluminum toxicity in degenerative disease.