Melatonin antagonizes apoptosis via receptor interaction in U937 monocytic cells.
Among the non-neurological functions of melatonin, much attention is being directed to the ability of melatonin to modulate the immune system, whose cells possess melatonin-specific receptors and biosynthetic enzymes. Melatonin controls cell behaviour by eliciting specific signal transduction actions after its interaction with plasma membrane receptors (MT(1), MT(2)); additionally, melatonin potently neutralizes free radicals. Melatonin regulates immune cell loss by antagonizing apoptosis. A major unsolved question is whether this is due to receptor involvement, or to radical scavenging considering that apoptosis is often dependent on oxidative alterations. Here, we provide evidence that on U937 monocytic cells, apoptosis is antagonized by melatonin by receptor interaction rather than by radical scavenging. First, melatonin and a set of synthetic analogues prevented apoptosis in a manner that is proportional to their affinity for plasma membrane receptors but not to their antioxidant ability. Secondly, melatonin's antiapoptotic effect required key signal transduction events including G protein, phospholipase C and Ca(2+) influx and, more important, it is sensitive to the specific melatonin receptor antagonist luzindole.
Radogna
Flavia
F
Dipartimento di Biologia, Università di Roma Tor Vergata, Rome, Italy.
Paternoster
Laura
L
Albertini
Maria Cristina
MC
Cerella
Claudia
C
Accorsi
Augusto
A
Bucchini
Anahi
A
Spadoni
Gilberto
G
Diamantini
Giuseppe
G
Tarzia
Giorgio
G
De Nicola
Milena
M
D'Alessio
Maria
M
Ghibelli
Lina
L
D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects; D006801:Humans; D008550:Melatonin / Q000031:analogs & derivatives / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D037342:Pertussis Toxin / Q000494:pharmacology; D044094:Receptors, Melatonin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014363:Tryptamines / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism; D020298:U937 Cells
D044094:Receptors, Melatonin; D014363:Tryptamines; C057154:luzindole; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D008550:Melatonin; D002118:Calcium