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Increased expression of diazepam binding inhibitor in human brain tumors
H Alho1, M Kolmer, T Harjuntausta
1Department of Biomedical Sciences, University of Tampere, Finland.
Abstract:
Benzodiazepines, which are in extensive clinical use, can regulate neoplastic growth via benzodiazepine receptors. We have studied the expression of the diazepam binding inhibitor (DBI) polypeptide, a putative endogenous ligand for benzodiazepine receptors in normal and pathological human brain. In normal brain, DBI immunoreactivity (IR) and mRNA were detected in all brain areas, with the highest levels in the cerebellum, amygdala, and hippocampus. In light and electron microscope immunohistochemistry, DBI-IR was only detected in glial and ependymal cells. In brain tumors, such as astrocytomas, glioblastomas and medulloblastomas, a much higher content of DBI-IR and -mRNA was found in normal tissues. The highest level of DBI expression was found in the most anaplastic tumors. DBI-IR was virtually undetectable in meningiomas and pituitary adenomas. The high expression of DBI in brain tumors might play a role in the neoplastic growth of glial cells via the mitochondrial benzodiazepine receptor, or it may be involved in the regulation of the high energy consumption of these tumors via acyl-CoA metabolism.
Insights
Diazepam binding inhibitor (DBI) is highly expressed in brain tumors, particularly in glial cell tumors. This suggests DBI may regulate neoplastic growth and energy metabolism in these cancers.
Area of Science:
- Neuroscience
- Oncology
- Molecular Biology
Background:
- Benzodiazepines influence neoplastic growth through benzodiazepine receptors.
- Diazepam binding inhibitor (DBI) is a potential endogenous ligand for these receptors.
Purpose of the Study:
- To investigate the expression of DBI polypeptide and its mRNA in normal and pathological human brain tissues.
- To correlate DBI expression levels with different types of brain tumors and their characteristics.
Main Methods:
- Immunohistochemistry (light and electron microscopy) was used to detect DBI immunoreactivity (IR).
- In situ hybridization was employed to analyze DBI mRNA expression.
- DBI expression was quantified in normal brain tissues and various brain tumors.
Main Results:
- DBI and its mRNA were found in all normal brain areas, with highest levels in the cerebellum, amygdala, and hippocampus.
- DBI-IR was localized to glial and ependymal cells in normal brain.
- Brain tumors (astrocytomas, glioblastomas, medulloblastomas) exhibited significantly higher DBI-IR and mRNA levels compared to normal tissues.
- DBI expression was highest in the most anaplastic tumors and undetectable in meningiomas and pituitary adenomas.
Conclusions:
- Elevated DBI expression in brain tumors suggests a role in glial cell neoplastic growth via mitochondrial benzodiazepine receptors.
- High DBI levels may also be involved in regulating the energy metabolism of brain tumors through acyl-CoA metabolism.