Gutierrez-Cuesta Javier, Tajes Marta, Jiménez Andrés, Coto-Montes Ana, Camins Antoni, Pallàs Mercè
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.
J Pineal Res. 2008 Nov;45(4):497-505. doi: 10.1111/j.1600-079X.2008.00626.x. Epub 2008 Aug 13.
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.
我们研究了褪黑素对三组小鼠促生存过程的影响。研究对象为10月龄未经处理的衰老加速小鼠（SAMP8）、经褪黑素处理的SAMP8小鼠以及未经处理的衰老加速抗性小鼠（SAMR1）。从出生后第一个月末至第九个月末，通过饮用水给予小鼠褪黑素（10 mg/kg）或赋形剂（0.066%乙醇）。检测Akt/Erk1-2信号通路及其下游靶点的差异，结果发现除β-连环蛋白外，未观察到显著变化。然而，SAMP8小鼠中沉默调节蛋白1的表达显著低于SAMR1小鼠。此外，SAMP8小鼠中乙酰化p53和核因子κB的表达低于SAMR1小鼠。褪黑素可防止这些变化。此外，未经处理的SAMP8小鼠中α-分泌酶的浓度/表达较低，淀粉样β蛋白聚集体（Aβ）的浓度/表达较高。同样，SAMP8小鼠中Bid的水平较高，而Bcl-2(XL)的水平较低。褪黑素可减轻所有这些变化。我们得出结论，褪黑素可改善与年龄相关的神经过程损伤中的促生存信号并减少促死亡信号。
