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Melatonin Reduces Apoptosis Induced by Calcium Signaling in Human Leukocytes: Evidence for the Involvement of Mitochondria and Bax Activation

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Abstract

We have evaluated the effect of melatonin on apoptosis evoked by increases in [Ca2+] c in human leukocytes. Our results show that treatment of neutrophils with the calcium mobilizing agonist FMLP or the specific inhibitor of calcium reuptake thapsigargin induced a transient increase in [Ca2+] c . Our results also show that FMLP and thapsigargin increased caspase-9 and -3 activities and the active forms of both caspases. The effect of FMLP and thapsigargin on caspase activation was time-dependent. Similar results were obtained when lymphocytes were stimulated with thapsigargin. This stimulatory effect was accompanied by induction of mPTP, activation of the proapoptotic protein Bax and release of cytochrome c. However, when leukocytes were pretreated with melatonin, all of the apoptotic features indicated above were significantly reversed. Our results suggest that melatonin reduces caspase-9 and -3 activities induced by increases in [Ca2+] c in human leukocytes, which are produced through the inhibition of both mPTP and Bax activation.

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Acknowledgement

This work was supported by MEC-DGI and Junta de Extremadura grants BFU2007-60091 and PRI07-A024, respectively. I. B. received a grant from Junta de Extremadura (PRE06070). P. C. R. is supported by the MEC-Ramón & Cajal program (RYC-2007-00349).

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Authors and Affiliations

  1. Department of Physiology, University of Extremadura, 06071, Badajoz, Spain

    Javier Espino, Ignacio Bejarano, Pedro C. Redondo, Juan A. Rosado, Carmen Barriga, José A. Pariente & Ana B. Rodríguez

  2. Department of Cellular and Structural Biology, The University of Texas Health Sciences Center, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA

    Russel J. Reiter

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  1. Javier Espino
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  2. Ignacio Bejarano
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  3. Pedro C. Redondo
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Correspondence to José A. Pariente.

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Espino, J., Bejarano, I., Redondo, P.C. et al. Melatonin Reduces Apoptosis Induced by Calcium Signaling in Human Leukocytes: Evidence for the Involvement of Mitochondria and Bax Activation. J Membrane Biol 233, 105–118 (2010). https://doi.org/10.1007/s00232-010-9230-0

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