Evaluation of potential pro-survival pathways regulated by melatonin in a murine senescence model.
We examined the effect of melatonin on pro-survival processes in three groups of mice. Untreated senescence-accelerated mice (SAMP8), melatonin-treated SAMP8 and untreated senescence-accelerated resistant mice (SAMR1) of 10 months old were studied. Melatonin (10 mg/kg) or vehicle (ethanol at 0.066%) was supplied in the drinking water from the end of the first month until the end of the ninth month of life. Differences in the Akt/Erk1-2 pathway and downstream targets were examined and no significant changes were observed, except for beta-catenin. However, sirtuin 1 expression was significantly lower in SAMP8 than in SAMR1. In addition, acetylated p53 and NFkappaB expression were lower in SAMP8 than in SAMR1. These changes were prevented by melatonin. Moreover, the concentration/expression of alpha-secretase was lower and that of amyloid beta aggregates (Abeta) was higher in untreated SAMP8 than in SAMR1. Likewise, the levels of Bid were higher, whereas Bcl-2(XL) levels were lower in SAMP8 than in SAMR1. Melatonin reduced all these changes. We conclude that melatonin improves pro-survival signals and reduces pro-death signals in age-related impairments of neural processes.
Gutierrez-Cuesta
Javier
J
Unitat de Farmacologia i Farmacognòsia Facultat de Farmàcia, Institut de Biomedicina (IBUB), Centros de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Universitat de Barcelona, Nucli Universitari de Pedralbes, Barcelona, Spain.
Tajes
Marta
M
Jiménez
Andrés
A
Coto-Montes
Ana
A
Camins
Antoni
A
Pallàs
Mercè
M
D000375:Aging / Q000187:drug effects*; D019588:Aging, Premature; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects*; D002474:Cell-Free System; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D056564:Sirtuin 1; D037761:Sirtuins / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
D016229:Amyloid beta-Peptides; D051023:BH3 Interacting Domain Death Agonist Protein; C494815:Bid protein, mouse; D016328:NF-kappa B; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; D051057:Proto-Oncogene Proteins c-akt; D048052:Mitogen-Activated Protein Kinase 3; D053829:Amyloid Precursor Protein Secretases; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D037761:Sirtuins; D008550:Melatonin