Melatonin prevents apoptosis and enhances HSP27 mRNA expression induced by heat shock in HL-60 cells: Possible involvement of the MT₂ receptor

Previous studies have reported that melatonin protects cells and tissues against stressful stimuli. In the present study using HL-60 cells, we show that cells acquire increased resistance to apoptosis normally induced by heat shock when they are incubated with melatonin. This effect of melatonin is saturable at nanomolar concentrations and appears to be mediated by the MT₂ subtype melatonin receptor. The high affinity melatonin receptor agonist, 2-iodomelatonin, reproduced the melatonin effect while it was fully blocked by the selective MT₂ antagonist 4-phenyl-2-propionamidotetraline. The melatonin response to heat shock-induced apoptosis was pertussis toxin sensitive and, interestingly, the non-selective MT₁/MT₂ melatonin receptor ligand luzindole was found to display agonistic activity. Furthermore, we provide evidence that melatonin enhanced HSP27 mRNA expression as a result of heat shock - HSP27, is known to play an important role in the defense of cells against apoptosis induced by stressful agents. Together, these results demonstrate that melatonin, likely via receptor mechanisms, interferes with the apoptotic pathway activated by heat shock.