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Estrogen receptor ligands affect mitochondrial activity in SH-SY5Y human neuroblastoma cells
Peter B Simpson1, Anthony J Woollacott, Zahid Moneer
1Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK.
Abstract:
We have studied the pharmacological regulation of mitochondrial activity in a human neuroblastoma cell line. Cyclosporin A was found to directly alter mitochondrial membrane potential and to decrease mitochondrial permeability as measured using calcein. The estrogen receptor ligands tamoxifen, nafoxidine and clomiphene were identified as agents which affect mitochondrial membrane potential in a cyclosporin A-like manner. Also when mitochondrial permeability was measured using calcein, tamoxifen, nafoxidine and clomiphene were effective in inhibiting dye loss from mitochondria. Nafoxidine and cyclosporin A inhibit effects of mastoparan on SH-SY5Y mitochondria. These studies indicate that estrogen receptor ligands appear to affect mitochondria in a cyclosporin A-like manner in human neuroblastoma cells.
Insights
Estrogen receptor ligands like tamoxifen affect mitochondrial membrane potential and permeability in neuroblastoma cells, similar to Cyclosporin A. These findings reveal a novel mechanism for regulating mitochondrial function.
Area of Science:
- Neuroscience
- Pharmacology
- Cell Biology
Background:
- Mitochondrial function is crucial for neuronal health.
- Pharmacological agents can modulate mitochondrial activity.
- Estrogen receptor ligands have diverse cellular effects.
Purpose of the Study:
- To investigate the effects of Cyclosporin A and estrogen receptor ligands on mitochondrial activity in human neuroblastoma cells.
- To determine if estrogen receptor ligands mimic Cyclosporin A's effects on mitochondria.
Main Methods:
- Utilized a human neuroblastoma cell line (SH-SY5Y).
- Measured mitochondrial membrane potential.
- Assessed mitochondrial permeability using calcein dye.
- Investigated the effects of Cyclosporin A, tamoxifen, nafoxidine, and clomiphene.
Main Results:
- Cyclosporin A directly altered mitochondrial membrane potential and decreased mitochondrial permeability.
- Tamoxifen, nafoxidine, and clomiphene affected mitochondrial membrane potential similarly to Cyclosporin A.
- These ligands also inhibited calcein dye loss, indicating reduced mitochondrial permeability.
- Nafoxidine and Cyclosporin A counteracted mastoparan's effects on mitochondria.
Conclusions:
- Estrogen receptor ligands exhibit Cyclosporin A-like effects on mitochondrial membrane potential and permeability in neuroblastoma cells.
- This suggests a novel pathway for pharmacological regulation of mitochondrial function by estrogen receptor ligands.