Hydroxytyrosol increases norepinephrine transporter function in pheochromocytoma cells
| Autor: | Sabine Hilfiker, Arjan Geerlings, Berta Luzón-Toro |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Cancer Research
medicine.medical_specialty Antioxidant medicine.medical_treatment Tritium 3-Iodobenzylguanidine PC12 Cells Norepinephrine (medication) Pheochromocytoma Norepinephrine chemistry.chemical_compound Internal medicine medicine Animals Radiology Nuclear Medicine and imaging Norepinephrine Plasma Membrane Transport Proteins biology Phenylethyl Alcohol medicine.disease Rats Endocrinology chemistry Norepinephrine transporter biology.protein Molecular Medicine Hydroxytyrosol Intracellular medicine.drug |
| Zdroj: | Nuclear Medicine and Biology. 35:801-804 |
| ISSN: | 0969-8051 |
| DOI: | 10.1016/j.nucmedbio.2008.07.005 |
| Popis: | Introduction The norepinephrine transporter is responsible for the intracellular uptake of 131 I- iodometaiodobenzylguanidine ( 131 I-MIBG), which is used for the diagnostic localization and treatment of pheochromocytomas as well as other tumors such as neuroblastomas and carcinoids. This agent is variably delivered into tumor cells by the norepinephrine transporter, but few studies have shown treatments that work to increase norepinephrine transporter activity. The objective of the present study was to test the possible beneficial effects of hydroxytyrosol in enhancing norepinephrine transporter function, which may have implications for its combined use with 131 I-MIBG in the diagnosis and treatment of pheochromocytomas. Methods Rat pheochromocytoma PC12 cells were labeled with [ 3 H]-norepinephrine in the presence or absence of different concentrations of hydroxytyrosol, a naturally occurring compound with strong antioxidant properties, followed by measurements of uptake and release of radiolabeled norepinephrine. Results Hydroxytyrosol pronouncedly increased norepinephrine transporter activity, with the rapid onset excluding effects on norepinephrine transporter expression levels. Concomitant with increased norepinephrine transporter activity, hydroxytyrosol caused a decrease of both spontaneous and evoked norepinephrine release, indicating that it affects pre-existing plasma membrane-associated norepinephrine transporter, rather than the incorporation of novel norepinephrine transporter molecules into the plasma membrane. Conclusion Hydroxytyrosol potently enhances norepinephrine transporter activity in pheochromocytoma PC12 cells, suggesting that combinatorial therapy employing hydroxytyrosol may improve the effectiveness of 131 I-MIBG as a diagnosis and treatment modality. |
| Databáze: | OpenAIRE |
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