Estrogen receptor ligands affect mitochondrial activity in SH-SY5Y human neuroblastoma cells.
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.
Simpson
Peter B
PB
Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK.
Woollacott
Anthony J
AJ
Moneer
Zahid
Z
Rand
Vikki
V
Seabrook
Guy R
GR
D016572:Cyclosporine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D008024:Ligands; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009447:Neuroblastoma / Q000378:metabolism*; D010539:Permeability / Q000187:drug effects; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D008024:Ligands; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D016572:Cyclosporine