Nanomolar aluminum induces pro-inflammatory and pro-apoptotic gene expression in human brain cells in primary culture

摘要: Aluminum, the most abundant neurotoxic metal in our biosphere, has been implicated etiology of several neurodegenerative disorders including Alzheimer's disease (AD). To further understand aluminum's influence on gene expression, we examined total messenger RNA levels untransformed human neural cells exposed to 100 nanomolar aluminum sulfate using high density DNA microarrays that interrogate expression every gene. Preliminary data indicate altered levels, 17/24 (70.8%) aluminum-affected genes, and 7/8 (87.5%) aluminum-induced genes exhibit patterns similar those observed AD. The seven found be significantly up-regulated by encode pro-inflammatory or pro-apoptotic signaling elements, NF-kappaB subunits, interleukin-1beta precursor, cytosolic phospholipase A2, cyclooxygenase-2, beta-amyloid precursor protein DAXX, a regulatory known induce apoptosis repress transcription. promoters are enriched binding sites for stress-inducible transcription factors HIF-1 NF-kappaB, suggesting role aluminum, driving atypical, expression. effect specific stress-related brain clearly warrant investigation.