Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Jan 27;6(1):e15965.
doi: 10.1371/journal.pone.0015965.

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

Valentina Gatta  1 , Denise Drago, Karina Fincati, Maria Teresa Valenti, Luca Dalle Carbonare, Stefano L Sensi, Paolo Zatta
Affiliations

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

Valentina Gatta et al. PLoS One. .

Abstract

Background: 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.

Methodology: In this study, employing a microarray analysis of 35,129 genes, we investigated the effects induced by the exposure to the Aβ(1-42)-Al (Aβ-Al) complex on the gene expression profile of the neuronal-like cell line, SH-SY5Y.

Principal findings: The microarray assay indicated that, compared to Aβ or Al alone, exposure to Aβ-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: Aβ-Al appears to be largely involved in the molecular machinery that regulates neuronal as well as synaptic dysfunction and loss. Aβ-Al seems critical in modulating key AD-related pathways such as glutamatergic transmission, Ca(2+) homeostasis, oxidative stress, inflammation, and neuronal apoptosis.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Biological functions associated with genes selectively changed by the exposure to the Aβ-Al complex.
Bar charts show key biological functions associated with genes found to be selectively either overexpressed (A) or downexpressed (B) in SH-SY5Y cells exposed to Aβ-Al.
Figure 2
Figure 2. Top networks generated by IPA associated with genes selectively overexpressed by the exposure to the Aβ-Al complex.
Genes in red show increased expression in SH-SY5Y cells exposed to Aβ-Al when compared with untreated SH-SY5Y cells. Arrows indicate that a molecule acts on another while lines indicate that a molecule binds to another. Small histograms indicate changes in gene expression.
Figure 3
Figure 3. Top networks generated by IPA associated with genes selectively downexpressed by the exposure to the Aβ-Al complex.
Genes in green show decreased expression in SH-SY5Y cells exposed to Aβ-Al when compared with untreated SY5Y cells. Arrows indicate that a molecule acts on another while lines indicate that a molecule binds to another. Small histograms indicate changes in gene expression.
Figure 4
Figure 4. IPA-generated pathways associated with genes selectively over or downexpressed upon exposure to Aβ-Al: modulation of glutamatergic transmission and synaptic plasticity.
IPA-generated pathways as resulting from the analysis of gene changes in SH-SY5Y cells exposed to the Aβ-Al when compared with untreated SH-SY5Y cells. Overexpressed genes are depicted in red, downexpressed genes are in green while genes in white are the ones inferred by IPA.
Figure 5
Figure 5. IPA-generated pathways associated with genes selectively over or downexpressed upon exposure to Aβ-Al: modulation of Ca2+ homeostasis.
IPA-generated pathways as resulting from the analysis of gene changes in SH-SY5Y cells exposed to the Aβ-Al when compared with untreated SH-SY5Y cells. Overexpressed genes are depicted in red, downexpressed genes are in green while genes in white are the ones inferred by IPA.
Figure 6
Figure 6. Summary of genes, biological functions, and pathways associated with gene expression changes triggered by the exposure to the Aβ-Al complex in SH-SY5Y cells.
See this image and copyright information in PMC

References

    1. Lovell MA, Robertson JD, Teesdale WJ, Campbell JL, Markesbery WR. Copper, iron and zinc in Alzheimer's disease senile plaques. J Neurol Sci. 1998;158:47–52. - PubMed
    1. Good PF, Perl DP, Bierer LM, Schmeidler J. Selective accumulation of aluminum and iron in the neurofibrillary tangles of Alzheimer's disease: a laser microprobe (LAMMA) study. Ann Neurol. 1992;31:286–292. - PubMed
    1. Liu G, Huang W, Moir RD, Vanderburg CR, Lai B, et al. Metal exposure and Alzheimer's pathogenesis. J Struct Biol. 2006;155:45–51. - PubMed
    1. Sensi SL, Paoletti P, Bush AI, Sekler I. Zinc in the physiology and pathology of the CNS. Nat Rev Neurosci. 2009;10:780–791. - PubMed
    1. House E, Collingwood J, Khan A, Korchazkina O, Berthon G, et al. Aluminium, iron, zinc and copper influence the in vitro formation of amyloid fibrils of Abeta42 in a manner which may have consequences for metal chelation therapy in Alzheimer's disease. J Alzheimers Dis. 2004;6:291–301. - PubMed

Publication types