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Microarray analysis on human neuroblastoma cells exposed to aluminum, ?(1-42)-amyloid or the ?(1-42)-amyloid aluminum complex.

ABSTRACT: BACKGROUND: A typical pathological feature of Alzheimer's disease (AD) is the appearance in the brain of senile plaques made up of ?-amyloid (A?) and neurofibrillary tangles. AD is also associated with an abnormal accumulation of some metal ions, and we have recently shown that one of these, aluminum (Al), plays a relevant role in affecting A? aggregation and neurotoxicity. METHODOLOGY: In this study, employing a microarray analysis of 35,129 genes, we investigated the effects induced by the exposure to the A?(1-42)-Al (A?-Al) complex on the gene expression profile of the neuronal-like cell line, SH-SY5Y. PRINCIPAL FINDINGS: The microarray assay indicated that, compared to A? or Al alone, exposure to A?-Al complex produced selective changes in gene expression. Some of the genes selectively over or underexpressed are directly related to AD. A further evaluation performed with Ingenuity Pathway analysis revealed that these genes are nodes of networks and pathways that are involved in the modulation of Ca(2+) homeostasis as well as in the regulation of glutamatergic transmission and synaptic plasticity. CONCLUSIONS AND SIGNIFICANCE: A?-Al appears to be largely involved in the molecular machinery that regulates neuronal as well as synaptic dysfunction and loss. A?-Al seems critical in modulating key AD-related pathways such as glutamatergic transmission, Ca(2+) homeostasis, oxidative stress, inflammation, and neuronal apoptosis.

SUBMITTER: Gatta V

PROVIDER: S-EPMC3029275 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Microarray analysis on human neuroblastoma cells exposed to aluminum, β(1-42)-amyloid or the β(1-42)-amyloid aluminum complex.

Gatta Valentina V Drago Denise D Fincati Karina K Valenti Maria Teresa MT Dalle Carbonare Luca L Sensi Stefano L SL Zatta Paolo P

PloS one 20110127 1

<h4>Background</h4>A typical pathological feature of Alzheimer's disease (AD) is the appearance in the brain of senile plaques made up of β-amyloid (Aβ) and neurofibrillary tangles. AD is also associated with an abnormal accumulation of some metal ions, and we have recently shown that one of these, aluminum (Al), plays a relevant role in affecting Aβ aggregation and neurotoxicity.<h4>Methodology</h4>In this study, employing a microarray analysis of 35,129 genes, we investigated the effects induc ...[more]

PMID: 21298039

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Project description:BackgroundMaleic acid is a multi-functional chemical widely used in the field of industrial chemistry for producing food additives and food contact materials. As maleic acid may contaminate food by the release from food packages or intentional addition, it raises the concern about the effects of excessive dietary exposure to maleic acid on human health. However, the influence of maleic acid on human health has not been thoroughly studied. In silico toxicogenomics approaches have found the association between maleic acid and nervous system disease in human. The aim of this study is to experimentally explore the effects of maleic acid on human neuronal cells.MethodsA microarray-based transcriptome profiling was performed to offer a better understanding of the effects of maleic acid on human health. Gene expression profiles of human neuroblastoma SH-SY5Y cells exposed to three concentrations of maleic acid (10, 50, and 100 μM) for 24 h were analyzed. Genes which were differentially expressed in dose-dependent manners were identified and further analyzed with an enrichment analysis. The expression profile of selected genes related to the inferred functional changes was validated using quantitative polymerase chain reaction (qPCR). Specific fluorescence probes were applied to observe the inferred functional changes in maleic acid-treated neuronal cells.ResultsA total of 316 differentially expressed genes (141 upregulated and 175 downregulated) were identified in response to the treatment of maleic acid. The enrichment analysis showed that DNA binding and metal ion binding were the significant molecular functions (MFs) of the neuronal cells affected by maleic acid. Maleic acid exposure decreased the expression of genes associated with calcium and thiol levels of the cells in a dose-dependent manner. The levels of intracellular calcium and thiol levels were also affected by maleic acid dose-dependent.DiscussionThe exposure to maleic acid is found to decrease the cellular calcium and thiol levels in human neuronal cells at both transcriptional and functional levels. This study reported the first transcriptomic profiling of human neuronal cells treated with maleic acid. It is also the first experimental validation of chemical effects predicted by in silico toxicogenomics approaches. The proposed approach may be useful in understanding the potential effects of other poorly characterized chemicals on human health.

Dataset Information

Microarray analysis on human neuroblastoma cells exposed to aluminum, ?(1-42)-amyloid or the ?(1-42)-amyloid aluminum complex.

Publications

Microarray analysis on human neuroblastoma cells exposed to aluminum, β(1-42)-amyloid or the β(1-42)-amyloid aluminum complex.

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