Metal specificity of an iron-responsive element in Alzheimer's APP mRNA 5'untranslated region, tolerance of SH-SY5Y and H4 neural cells to desferrioxamine, clioquinol, VK-28, and a piperazine chelator.
Metal specificity of an iron-responsive element in Alzheimer's APP mRNA 5'untranslated region, tolerance of SH-SY5Y and H4 neural cells to desferrioxamine, clioquinol, VK-28, and a piperazine chelator.
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DOI：
10.1007/978-3-211-33328-0_25
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发表时间：
2006
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影响因子：
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通讯作者：
Sanghamitra Bandyopadhyay;Xudong Huang;H. Cho;Nigel H. Greig;Moussa B. H. Youdim;Jack T. Rogers
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文献类型：
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作者：
Sanghamitra Bandyopadhyay;Xudong Huang;H. Cho;Nigel H. Greig;Moussa B. H. Youdim;Jack T. Rogers
铁在信息翻译水平上密切调节阿尔茨海默氏淀粉样前体蛋白（APP）基因的表达，其途径类似于铁在铁蛋白L-和H mrna的5 ‘非翻译区（5’UTRs）中铁响应元件对铁蛋白L-和H mrna翻译的控制。通过转染SH-SY5Y神经母细胞瘤细胞，我们测试了铁、铜和锌上调APP 5'UTR中IRE活性的相对效率。检测了去铁胺（高亲和力铁离子螯合剂）、氯喹诺（低亲和力铁/铜/锌螯合剂）、哌嗪-1（口服铁螯合剂）、VK-28（口服铁螯合剂）对APP 5'UTR定向翻译荧光素酶报告基因的相对调节作用。本文讨论了基于铁螯合的治疗策略，以减缓阿尔茨海默病（以及其他表现为铁失衡的神经系统疾病）的进展，并讨论了每种螯合剂对SH-SY5Y细胞和H4胶质母细胞瘤细胞的相对神经毒性作用。
Iron closely regulates the expression of the Alzheimer’s Amyloid Precursor Protein (APP) gene at the level of message translation by a pathway similar to iron control of the translation of the ferritin L- and H mRNAs by Iron-responsive Elements in their 5′untranslated regions (5′UTRs). Using transfection based assays in SH-SY5Y neuroblastoma cells we tested the relative efficiency by which iron, copper and zinc up-regulate IRE activity in the APP 5′UTR. Desferrioxamine (high affinity Fe3+chelator), (ii) clioquinol (low affinity Fe/Cu/Zn chelator), (iii) piperazine-1 (oral Fe chelator), (iv) VK-28 (oral Fe chelator), were tested for their relative modulation of APP 5′UTR directed translation of a luciferase reporter gene. Iron chelation based therapeutic strategies for slowing the progression of Alzheimer’s disease (and other neurological disorders that manifest iron imbalance) are discussed with regard to the relative neural toxic action of each chelator in SH-SY5Y cells and in H4 glioblastoma cells.