ALUMINUM, NEUROTOXICITY AND GENE EXPRESSION

Project: Research project

Description

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.
StatusActive
Effective start/end date1/1/85 → …

Funding

  • National Institutes of Health

Fingerprint

Aluminum
Gene Expression
Genes
Histones
DNA
ras Proteins
Cell Line
Neurofibrillary Tangles
Replication Origin
ras Genes
Intermediate Filaments
Interferon-beta
Microbial Drug Resistance
Neuroblastoma
Transfection
Chlorides
Ions
Rabbits
Neurons
Injections

ASJC

  • Medicine(all)