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

Abstract
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.
AuthorsJavier Cabrera, José Quintana, Russel J Reiter, Juan Loro, Félix Cabrera, Francisco Estévez
JournalJournal of pineal research (J Pineal Res) Vol. 35 Issue 4 Pg. 231-8 (Nov 2003) ISSN: 0742-3098 [Print] England
PMID14521627 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • HSP27 Heat-Shock Proteins
  • HSPB1 protein, human
  • Heat-Shock Proteins
  • Molecular Chaperones
  • Neoplasm Proteins
  • RNA, Messenger
  • Receptor, Melatonin, MT2
  • Melatonin
Topics
  • Apoptosis (physiology)
  • HL-60 Cells
  • HSP27 Heat-Shock Proteins
  • Heat-Shock Proteins (biosynthesis, genetics)
  • Hot Temperature
  • Humans
  • Melatonin (metabolism)
  • Molecular Chaperones
  • Neoplasm Proteins (biosynthesis, genetics)
  • RNA, Messenger (metabolism)
  • Receptor, Melatonin, MT2 (metabolism)

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