Melatonin reduces apoptosis induced by calcium signaling in human leukocytes: Evidence for the involvement of mitochondria and bax activation

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

Research output: Contribution to journalArticlepeer-review

91 Scopus citations

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 [Ca 2+] c in human leukocytes, which are produced through the inhibition of both mPTP and Bax activation.

Original languageEnglish (US)
Pages (from-to)105-118
Number of pages14
JournalJournal of Membrane Biology
Volume233
Issue number1-3
DOIs
StatePublished - Feb 1 2010

Keywords

  • Apoptosis
  • Caspases
  • Cytochrome c
  • Leukocytes
  • Melatonin
  • Mitochondria

ASJC Scopus subject areas

  • Biophysics
  • Physiology
  • Cell Biology

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