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Long-term morphine treatment increases Ku protein DNA end-binding activity
G Bakalkin1, T Yakovleva, M Melzig
1Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
Neuroreport
|July 7, 1997
Summary
Morphine exposure increased Ku protein activity in neuroendocrine cancer cells, an effect blocked by naloxone. This suggests opioids may influence gene regulation through the Ku protein.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Opioids, like morphine, are widely used analgesics with complex cellular effects.
- Neuroendocrine tumors, including small-cell lung carcinoma, can exhibit unique molecular responses to drug treatments.
- Understanding opioid-mediated gene regulation is crucial for managing treatment side effects and exploring therapeutic applications.
Purpose of the Study:
- To investigate the impact of morphine on transcription factor activity in neuroendocrine cell lines.
- To identify specific molecular mechanisms by which morphine might influence gene expression.
Main Methods:
- Exposure of human neuroblastoma (SH-SY5Y) and small-cell lung carcinoma (U1690) cells to morphine for varying durations (1 hour to 5 days).
- Assay of transcription factor activities, including AP-1, NF-kappa B, and YY1.
- Characterization of a morphine-induced DNA-binding factor using techniques like band shift assays, antibody inhibition, and analysis of subunit composition and molecular mass.
Main Results:
- Morphine treatment did not significantly alter the activity of AP-1, NF-kappa B, or YY1 transcription factors in either cell line.
- A five-day morphine exposure led to a twofold increase in the activity of a spermidine-activated, sequence-non-specific DNA-binding factor in U1690 cells.
- This DNA-binding factor was identified as the Ku protein, a component of DNA-dependent protein kinase, and its activation by morphine was reversible with naloxone.
Conclusions:
- Opioid administration, specifically morphine, can modulate the activity of the Ku protein in neuroendocrine cancer cells.
- The Ku protein, activated by spermidine and binding to DNA ends, is implicated in the cellular response to prolonged morphine exposure.
- This morphine-induced Ku protein activation may represent a novel pathway through which opioids influence gene regulation, potentially impacting cellular function and therapeutic outcomes.