Distinct roles of N-acetyl and 5-methoxy groups in the antiproliferative and neuroprotective effects of melatonin
| Autor: | Ricardo Letra-Vilela, Federico Herrera, Mariana Santa-Marta, Joana Branco-Santos, Ana M. Sanchez-Sanchez, Tiago F. Outeiro, Isaac Antolín, Carmen Rodríguez, Vanesa Martín, Ana Maia Rocha, Noelia Puente-Moncada |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Programmed cell death Antioxidant Cell Survival medicine.medical_treatment Glutamic Acid Biology Pharmacology Hippocampus Biochemistry Neuroprotection Antioxidants Cell Line 5-Methoxytryptamine Melatonin Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Endocrinology Autophagy medicine Animals Humans Molecular Biology Cell Proliferation Cell growth HEK293 Cells Neuroprotective Agents 030104 developmental biology chemistry Apoptosis hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Molecular and Cellular Endocrinology. 434:238-249 |
| ISSN: | 0303-7207 |
| DOI: | 10.1016/j.mce.2016.07.012 |
| Popis: | Melatonin (N-acetyl-5-methoxytryptamine) is a highly pleiotropic hormone with antioxidant, antiproliferative, oncolytic and neuroprotective properties. Here, we present evidence that the N-acetyl side chain plays a key role in melatonin's antiproliferative effect in HT22 and sw-1353 cells, but it does so at the expense of antioxidant and neuroprotective properties. Removal of the N-acetyl group enhances the antioxidant and neuroprotective properties of the indole, but it can lead to toxic methamphetamine-like effects in several cell lines. Inhibition of NFkB mimicked melatonin's antiproliferative and antioxidant effects, but not neuroprotection. Our results strongly suggest that neuroprotective and antiproliferative effects of melatonin rely on different parts of the molecule and are likely mediated by different mechanisms. We also predict that melatonin metabolism by target cells could determine whether melatonin inhibits cell proliferation, prevents toxicity or induces cell death (e.g. apoptosis or autophagy). These observations could have important implications for the rational use of melatonin in personalized medicine. |
| Databáze: | OpenAIRE |
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