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Bcl-2 expression regulates cell sensitivity to S100beta-mediated apoptosis
S Wang1, L E Rosengren, M Franlund
1Department of Anatomy and Cell Biology, Göteborg University, Medicinaregatan 5, 413 90, Göteborg, Sweden. shu.wang@anatcell.gu.se
Brain Research. Molecular Brain Research
|June 25, 1999
Summary
S100beta protein induces neuronal apoptosis, a process regulated by Bcl-2. Upregulation of S100beta and downregulation of Bcl-2 may contribute to Alzheimer's and Down's syndrome pathogenesis.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- S100beta protein is overexpressed in Alzheimer's disease and Down's syndrome.
- S100beta induces neuronal apoptosis at high concentrations.
- Intracellular regulators of S100beta-induced apoptosis are largely unknown.
Purpose of the Study:
- Investigate the role of the bcl-2 proto-oncogene in S100beta-induced apoptosis.
- Determine if Bcl-2 can modulate S100beta-mediated neuronal cell death.
Main Methods:
- Used human neuronal precursor NT2/D1 cells.
- Exposed cells to S100beta and analyzed apoptosis.
- Utilized gene transfer to elevate Bcl-2 levels.
- Differentiated cells with retinoic acid and assessed S100beta sensitivity.
- Used antisense oligonucleotides to downregulate Bcl-2.
Main Results:
- S100beta exposure led to apoptosis preceded by Bcl-2 downregulation.
- Elevated Bcl-2 levels repressed S100beta-induced cell death.
- Differentiated neurons with upregulated Bcl-2 were resistant to S100beta.
- Bcl-2 downregulation increased neuronal susceptibility to S100beta.
Conclusions:
- Apoptosis induced by S100beta signaling is regulated by Bcl-2.
- Combined S100beta upregulation and Bcl-2 downregulation may be crucial in Alzheimer's and Down's syndrome pathogenesis.