Melatonin is a modified tryptophan with potent biological activity, exerted by stimulation of specific plasma membrane (MT1/MT2) receptors, by lower affinity intracellular enzymatic targets (quinone reductase, calmodulin), or through its strong anti-oxidant ability. Scattered studies also report a perplexing pro-oxidant activity, showing that melatonin is able to stimulate production of intracellular reactive oxygen species (ROS). Here we show that on U937 human monocytes melatonin promotes intracellular ROS in a fast (<1 min) and transient (up to 5-6 h) way. Melatonin equally elicits its pro-radical effect on a set of normal or tumor leukocytes; intriguingly, ROS production does not lead to oxidative stress, as shown by absence of protein carbonylation, maintenance of free thiols, preservation of viability and regular proliferation rate. ROS production is independent from MT1/MT2 receptor interaction, since a) requires micromolar (as opposed to nanomolar) doses of melatonin; b) is not contrasted by the specific MT1/MT2 antagonist luzindole; c) is not mimicked by a set of MT1/MT2 high affinity melatonin analogues. Instead, chlorpromazine, the calmodulin inhibitor shown to prevent melatonin-calmodulin interaction, also prevents melatonin pro-radical effect, suggesting that the low affinity binding to calmodulin (in the micromolar range) may promote ROS production.

Radogna, F., Paternoster, L., DE NICOLA, M., Cerella, C., Ammendola, S., Bedini, A., et al. (2009). Rapid and transient stimulation of intracellular reactive oxygen species by melatonin in normal and tumor leukocytes. TOXICOLOGY AND APPLIED PHARMACOLOGY, 239(1), 37-45 [10.1016/j.taap.2009.05.012].

Rapid and transient stimulation of intracellular reactive oxygen species by melatonin in normal and tumor leukocytes

RADOGNA, FLAVIA;DE NICOLA, MILENA;AQUILANO, KATIA;CIRIOLO, MARIA ROSA;GHIBELLI, LINA
2009-01-01

Abstract

Melatonin is a modified tryptophan with potent biological activity, exerted by stimulation of specific plasma membrane (MT1/MT2) receptors, by lower affinity intracellular enzymatic targets (quinone reductase, calmodulin), or through its strong anti-oxidant ability. Scattered studies also report a perplexing pro-oxidant activity, showing that melatonin is able to stimulate production of intracellular reactive oxygen species (ROS). Here we show that on U937 human monocytes melatonin promotes intracellular ROS in a fast (<1 min) and transient (up to 5-6 h) way. Melatonin equally elicits its pro-radical effect on a set of normal or tumor leukocytes; intriguingly, ROS production does not lead to oxidative stress, as shown by absence of protein carbonylation, maintenance of free thiols, preservation of viability and regular proliferation rate. ROS production is independent from MT1/MT2 receptor interaction, since a) requires micromolar (as opposed to nanomolar) doses of melatonin; b) is not contrasted by the specific MT1/MT2 antagonist luzindole; c) is not mimicked by a set of MT1/MT2 high affinity melatonin analogues. Instead, chlorpromazine, the calmodulin inhibitor shown to prevent melatonin-calmodulin interaction, also prevents melatonin pro-radical effect, suggesting that the low affinity binding to calmodulin (in the micromolar range) may promote ROS production.
2009
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/10 - BIOCHIMICA
Settore MED/49 - SCIENZE TECNICHE DIETETICHE APPLICATE
English
Con Impact Factor ISI
Melatonin; reactive oxygen species; Leukocytes
Radogna, F., Paternoster, L., DE NICOLA, M., Cerella, C., Ammendola, S., Bedini, A., et al. (2009). Rapid and transient stimulation of intracellular reactive oxygen species by melatonin in normal and tumor leukocytes. TOXICOLOGY AND APPLIED PHARMACOLOGY, 239(1), 37-45 [10.1016/j.taap.2009.05.012].
Radogna, F; Paternoster, L; DE NICOLA, M; Cerella, C; Ammendola, S; Bedini, A; Tarzia, G; Aquilano, K; Ciriolo, Mr; Ghibelli, L
Articolo su rivista
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/15550
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