Influence of aging and growth hormone on different members of the NFkB family and IkB expression in the heart from a murine model of senescence-accelerated aging

Influence of aging and growth hormone on different members of the NFkB family and IkB expression in the heart from a murine model of senescence-accelerated aging
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DOI:
10.1016/j.exger.2015.11.005
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发表时间:
2016-01-01
影响因子:
3.9
通讯作者:
Tresguerres, J. A. F.
Tresguerres, J. A. F.
中科院分区:
医学2区
文献类型:
--
作者:
Forman, K.;Vara, E.;Tresguerres, J. A. F.

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炎症与几种病理过程有关。本研究的目的是通过Western blot研究加速衰老小鼠模型(SAM模型)心脏中核因子κ b不同亚基(NFkBp65、p50、p105、p52、p100)的蛋白表达以及IkB β和α的蛋白表达。此外,我们还研究了NFkB的一些同工异构体(NFkBp65、p50、p52)从细胞质到细胞核的易位和ATP的含量。此外,我们研究了生长激素(GH)的慢性管理对这些年龄相关参数的影响。选取2月龄和10月龄的SAMP8和SAMR1小鼠(n = 30)。实验动物分为5个实验组:2只老龄未处理组(SAMP8/SAMR1), 2只年轻对照组(SAMP8/SAMR1)和1只GH处理老龄组(SAMP8)。在研究参数中发现了与年龄相关的变化。我们发现老龄SAMP8小鼠ATP水平含量下降,核因子kappa B p50、p52和p65从细胞质转移到细胞核,同时IKB蛋白减少。p100和p105随年龄变化无明显差异。在SAMR1动物中没有记录到明显的变化。生长激素治疗在老年SAMP8小鼠中显示出有益的效果,诱导ATP水平的增加并抑制一些NFkB亚基(如p52)的易位。我们的研究结果支持NFkB激活与老年SAMP8小鼠细胞凋亡和促炎状态的增强之间的关系,并表明GH治疗具有选择性的有益作用,能够部分减少这些小鼠心脏中某些有害变化的发生率。(C) 2015爱思唯尔公司版权所有。
Inflammation is related to several pathological processes. The aim of this study was to investigate the protein expression of the different subunits of the nuclear factor Kappa b (NFkBp65, p50, p105, p52, p100) and the protein expressions of IkB beta and alpha in the hearts from a murine model of accelerated aging (SAM model) by Western blot. In addition, the translocation of some isoforms of NFkB from cytosol to nuclei (NFkBp65, p50, p52) and ATP level content was studied. In addition we investigated the effect of the chronic administration of growth hormone (GH) on these age-related parameters. SAMP8 and SAMR1 mice of 2 and 10 months of age were used (n = 30). Animals were divided into five experimental groups: 2 old untreated (SAMP8/SAMR1), 2 young control (SAMP8/SAMR1) and one GH treated-old groups (SAMP8). Age-related changes were found in the studied parameters. We were able to see decreases of ATP level contents and the translocation of the nuclear factor kappa B p50, p52 and p65 from cytosol to nuclei in old SAMP8 mice together with a decrease of IKB proteins. However p100 and p105 did not show differences with aging. No significant changes were recorded in SAMR1 animals. GH treatment showed beneficial effects in old SAMP8 mice inducing an increase in ATP levels and inhibiting the translocation of some NFkB subunits such as p52. Our results supported the relation of NFkB activation with enhanced apoptosis and pro-inflammatory status in old SAMP8 mice and suggested a selective beneficial effect of the GH treatment, which was able to partially reduce the incidence of some deleterious changes in the heart of those mice. (C) 2015 Elsevier Inc. All rights reserved.