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Induction of beta-amyloid precursor protein isoform mRNAs by bFGF in astrocytes
Abstract:
All three major transcripts of beta-amyloid precursor protein (APP) were expressed in astrocytes. The ratio for APP695, APP751 and APP770 isoform mRNAs being 1:4:2. Treatment with bFGF and EGF produced upregulation of APP mRNAs in cultured astrocytes in varying proportions. In comparison with controls, increases in APP mRNAs in bFGF and EGF treated groups were about 4.5 and 2 fold, respectively. The elevation in mRNAs of KPI-containing isoforms APP751 and APP770 was relatively more than the elevation in mRNA of APP695 isoform. Our findings provide further evidence for the involvement of astrocytes in a cascade of events leading to the development of senile plaques in Alzheimer's disease and Down's syndrome.
Insights
Astrocytes express beta-amyloid precursor protein (APP) transcripts. Growth factors like bFGF and EGF upregulate APP mRNA, particularly KPI-containing isoforms, suggesting astrocyte involvement in Alzheimer's disease pathogenesis.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Beta-amyloid precursor protein (APP) is central to Alzheimer's disease pathology.
- APP exists in multiple mRNA transcripts, including APP695, APP751, and APP770.
- Astrocytes play a role in brain homeostasis and disease processes.
Purpose of the Study:
- To investigate the expression of different APP mRNA transcripts in astrocytes.
- To determine the effect of basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) on APP mRNA levels in astrocytes.
- To understand the differential regulation of APP isoforms by growth factors.
Main Methods:
- Primary astrocyte cultures were established.
- Quantitative analysis of APP695, APP751, and APP770 mRNA levels was performed.
- Cells were treated with bFGF and EGF, and subsequent changes in APP mRNA expression were measured.
Main Results:
- All three major APP mRNA transcripts (APP695, APP751, APP770) were detected in cultured astrocytes at a ratio of approximately 1:4:2.
- Treatment with bFGF and EGF led to a significant upregulation of total APP mRNAs.
- APP mRNA levels increased by approximately 4.5-fold with bFGF and 2-fold with EGF compared to controls.
- The upregulation of KPI-containing isoforms (APP751 and APP770) was proportionally greater than that of the APP695 isoform.
Conclusions:
- Astrocytes express and differentially regulate major APP mRNA isoforms.
- Growth factors like bFGF and EGF can modulate APP mRNA expression in astrocytes.
- These findings support the role of astrocytes in the molecular cascade leading to senile plaque formation in Alzheimer's disease and Down's syndrome.