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Melatonin is able to delay endoplasmic reticulum stress-induced apoptosis in leukocytes from elderly humans

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Abstract

The mechanisms regulating neutrophil apoptosis are basically unaffected by the aging process. However, a significant impairment of cell survival occurs in elderly individuals following neutrophil challenge with pro-inflammatory stimuli, such as granulocyte-macrophage colony-stimulating factor (GM-CSF). The goal of the present study was to prove the effects of melatonin supplementation on apoptosis induced by calcium signaling in human leukocytes from elderly volunteers. Treatments with the specific inhibitor of cytosolic calcium re-uptake, thapsigargin, and/or the calcium mobilizing agonist, N-formyl-methionyl-leucyl-phenylalanine (fMLP), induced mitochondrial membrane depolarization, caspase activation, phosphatidylserine (PS) externalization, and DNA fragmentation in leukocytes from both young and elderly volunteers, although such effects were much more evident in aged leukocytes. Importantly, melatonin treatment substantially preserved mitochondrial membrane potential, reversed caspase activation, reduced PS exposure and forestalled DNA fragmentation in leukocytes from both age groups. In conclusion, melatonin is able to delay endoplasmic reticulum stress-induced apoptosis in aged leukocytes and may counteract, at the cellular level, age-related degenerative phenomena linked to oxidative stress.

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Acknowledgements

This work was supported by Junta de Extremadura (PRI07-A024) and MEC-Fondo Social Europeo de Desarrollo Regional grants (BFU2007-60091 and BFU2010-15049). I. Bejarano and S.D. Paredes are beneficiaries of grants from Consejería de Economía, Comercio e Innovación – Fondo Social Europeo (Junta de Extremadura, PRE06070 and POS07012, respectively). J. Espino is beneficiary of grant from MEC (AP2009-0753).

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Authors and Affiliations

  1. Department of Physiology, Neuroimmunophysiology and Chrononutrition Research Group, Faculty of Science, University of Extremadura, 06006, Badajoz, Spain

    Javier Espino, Ignacio Bejarano, Sergio D. Paredes, Carmen Barriga, José A. Pariente & Ana B. Rodríguez

  2. Department of Cellular & Structural Biology, University of Texas Health Science Center, San Antonio, TX, USA

    Russel J. Reiter

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  1. Javier Espino
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  2. Ignacio Bejarano
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  7. Ana B. Rodríguez
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Correspondence to Ana B. Rodríguez.

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Espino, J., Bejarano, I., Paredes, S.D. et al. Melatonin is able to delay endoplasmic reticulum stress-induced apoptosis in leukocytes from elderly humans. AGE 33, 497–507 (2011). https://doi.org/10.1007/s11357-010-9194-0

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  • DOI: https://doi.org/10.1007/s11357-010-9194-0

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