PMID- 21470303
OWN - NLM
STAT- MEDLINE
DCOM- 20111202
LR  - 20131121
IS  - 1600-079X (Electronic)
IS  - 0742-3098 (Linking)
VI  - 51
IP  - 2
DP  - 2011 Sep
TI  - Protective effect of melatonin against human leukocyte apoptosis induced by 
      intracellular calcium overload: relation with its antioxidant actions.
PG  - 195-206
LID - 10.1111/j.1600-079X.2011.00876.x [doi]
AB  - 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.
CI  - (c) 2011 John Wiley & Sons A/S.
FAU - Espino, Javier
AU  - Espino J
AD  - Department of Physiology, Faculty of Science, University of Extremadura, Badajoz, 
      Spain.
FAU - Bejarano, Ignacio
AU  - Bejarano I
FAU - Paredes, Sergio D
AU  - Paredes SD
FAU - Barriga, Carmen
AU  - Barriga C
FAU - Rodriguez, Ana B
AU  - Rodriguez AB
FAU - Pariente, Jose A
AU  - Pariente JA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110407
PL  - England
TA  - J Pineal Res
JT  - Journal of pineal research
JID - 8504412
RN  - 0 (Chelating Agents)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Free Radical Scavengers)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Ru 360)
RN  - 0 (Ruthenium Compounds)
RN  - 526U7A2651 (Egtazic Acid)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - 67526-95-8 (Thapsigargin)
RN  - 91416-19-2 (5,5'-dimethyl-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetate)
RN  - JL5DK93RCL (Melatonin)
RN  - SY7Q814VUP (Calcium)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Adult
MH  - Apoptosis/*drug effects
MH  - Calcium/*metabolism
MH  - Chelating Agents/pharmacology
MH  - DNA Fragmentation/drug effects
MH  - Egtazic Acid/analogs & derivatives/pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - Female
MH  - Free Radical Scavengers/*pharmacology
MH  - Humans
MH  - Leukocytes/cytology/*metabolism
MH  - Male
MH  - Melatonin/*pharmacology
MH  - Middle Aged
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - Reactive Oxygen Species/metabolism
MH  - Ruthenium Compounds/pharmacology
MH  - Thapsigargin/pharmacology
EDAT- 2011/04/08 06:00
MHDA- 2011/12/13 00:00
CRDT- 2011/04/08 06:00
PHST- 2011/04/08 06:00 [entrez]
PHST- 2011/04/08 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
AID - 10.1111/j.1600-079X.2011.00876.x [doi]
PST - ppublish
SO  - J Pineal Res. 2011 Sep;51(2):195-206. doi: 10.1111/j.1600-079X.2011.00876.x. Epub 
      2011 Apr 7.