Journal of Pineal Research

Volume 51, Issue 2 p. 195-206

Protective effect of melatonin against human leukocyte apoptosis induced by intracellular calcium overload: relation with its antioxidant actions

Javier Espino,

Javier Espino

Department of Physiology, Neuroimmunophysiology and Chrononutrition Research Group, Faculty of Science, University of Extremadura, Badajoz, Spain

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Ignacio Bejarano,

Ignacio Bejarano

Department of Physiology, Neuroimmunophysiology and Chrononutrition Research Group, Faculty of Science, University of Extremadura, Badajoz, Spain

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Sergio D. Paredes,

Sergio D. Paredes

Department of Physiology, Neuroimmunophysiology and Chrononutrition Research Group, Faculty of Science, University of Extremadura, Badajoz, Spain

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Carmen Barriga,

Carmen Barriga

Department of Physiology, Neuroimmunophysiology and Chrononutrition Research Group, Faculty of Science, University of Extremadura, Badajoz, Spain

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Ana B. Rodríguez,

Ana B. Rodríguez

Department of Physiology, Neuroimmunophysiology and Chrononutrition Research Group, Faculty of Science, University of Extremadura, Badajoz, Spain

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José A. Pariente,

José A. Pariente

Department of Physiology, Neuroimmunophysiology and Chrononutrition Research Group, Faculty of Science, University of Extremadura, Badajoz, Spain

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Javier Espino,

Javier Espino

Department of Physiology, Neuroimmunophysiology and Chrononutrition Research Group, Faculty of Science, University of Extremadura, Badajoz, Spain

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Ignacio Bejarano,

Ignacio Bejarano

Department of Physiology, Neuroimmunophysiology and Chrononutrition Research Group, Faculty of Science, University of Extremadura, Badajoz, Spain

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Sergio D. Paredes,

Sergio D. Paredes

Department of Physiology, Neuroimmunophysiology and Chrononutrition Research Group, Faculty of Science, University of Extremadura, Badajoz, Spain

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Carmen Barriga,

Carmen Barriga

Department of Physiology, Neuroimmunophysiology and Chrononutrition Research Group, Faculty of Science, University of Extremadura, Badajoz, Spain

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Ana B. Rodríguez,

Ana B. Rodríguez

Department of Physiology, Neuroimmunophysiology and Chrononutrition Research Group, Faculty of Science, University of Extremadura, Badajoz, Spain

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José A. Pariente,

José A. Pariente

Department of Physiology, Neuroimmunophysiology and Chrononutrition Research Group, Faculty of Science, University of Extremadura, Badajoz, Spain

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First published: 02 March 2011

https://doi.org/10.1111/j.1600-079X.2011.00876.x

Citations: 78

Address reprint requests to Dr. José Antonio Pariente, Department of Physiology, Faculty of Science, University of Extremadura, 06006 Badajoz, Spain.
E-mail: [email protected]

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Abstract

Abstract: Apoptosis or programmed cell death plays a critical role in both inflammatory and immune responses. Recent evidence demonstrates that control of leukocyte apoptosis is one of the most striking immune system-related roles of melatonin. For this reason, this study evaluated the protective effects of melatonin on human leukocyte apoptosis induced by sustained cytosolic calcium increases. Such protective effects are likely mediated by melatonin’s free-radical scavenging actions. Treatments with the specific inhibitor of cytosolic calcium re-uptake, thapsigargin (TG), and/or the calcium-mobilizing agonist, N-formyl-methionyl-leucyl-phenylalanine (FMLP), induced intracellular reactive oxygen species (ROS) production, caspase activation as well as DNA fragmentation in human leukocytes. Also, TG- and/or FMLP-induced apoptosis was dependent on both cytosolic calcium increases and calcium uptake into mitochondria, because when cells were preincubated with the cytosolic calcium chelator, dimethyl BAPTA, and the inhibitor of mitochondrial calcium uptake, Ru360, TG- and FMLP-induced apoptosis was largely inhibited. Importantly, melatonin treatment substantially prevented intracellular ROS production, reversed caspase activation, and forestalled DNA fragmentation induced by TG and FMLP. Similar results were obtained by preincubating the cells with another well-known antioxidant, i.e., N-acetyl-l-cysteine. To sum up, depletion of intracellular calcium stores induced by TG and/or FMLP triggers different apoptotic events in human leukocytes that are dependent on calcium signaling. The protective effects resulting from melatonin administration on leukocyte apoptosis likely depend on melatonin’s antioxidant action because we proved that this protection is melatonin receptor independent. These findings help to understand how melatonin controls apoptosis in cells of immune/inflammatory relevance.

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Volume51, Issue2

September 2011

Pages 195-206

Protective effect of melatonin against human leukocyte apoptosis induced by intracellular calcium overload: relation with its antioxidant actions

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Protective effect of melatonin against human leukocyte apoptosis induced by intracellular calcium overload: relation with its antioxidant actions

Abstract

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