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蛋白质组学数据显示,衰老加速小鼠血清中的自身抗体和甲胎蛋白增加,载脂蛋白 A-II 随时间减少。

Proteomic data show an increase in autoantibodies and alpha-fetoprotein and a decrease in apolipoprotein A-II with time in sera from senescence-accelerated mice.

机构信息

Beijing Institute of Pharmacology and Toxicology, Beijing, China.

出版信息

Braz J Med Biol Res. 2013 May;46(5):417-25. doi: 10.1590/1414-431X20132663. Epub 2013 Apr 12.

Abstract

We evaluated changes in levels by comparing serum proteins in senescence-accelerated mouse-prone 8 (SAMP8) mice at 2, 6, 12, and 15 months of age (SAMP8-2 m, -6 m, -12 m, -15 m) to age-matched SAM-resistant 1 (SAMR1) mice. Mice were sacrificed, and blood was analyzed by 2-dimensional electrophoresis combined with mass spectrometry. Five protein spots were present in all SAMP8 serum samples, but only appeared in SAMR1 samples at 15 months of age except for spot 3, which also showed a slight expression in SAMR1-12 m sera. Two proteins decreased in the sera from SAMP8-2 m, -6 m, and -12 m mice, and divided into 2 spots each in SAMP8-15 m sera. Thus, the total number of altered spots in SAMP8 sera was 7; of these, 4 were identified as Ig kappa chain V region (M-T413), chain A of an activity suppressing Fab fragment to cytochrome P450 aromatase (32C2_A), alpha-fetoprotein, and apolipoprotein A-II. M-T413 is a monoclonal CD4 antibody, which inhibits T cell proliferation. We found that M-T413 RNA level was significantly enhanced in splenocytes from SAMP8-2 m mice. This agreed with serum M-T413 protein alterations and a strikingly lower blood CD4+ T cell count in SAMP8 mice when compared to the age-matched SAMR1 mice, with the latter negatively correlating with serum M-T413 protein volume. Age-related changes in serum proteins favored an increase in autoantibodies and alpha-fetoprotein and a decrease of apolipoprotein A-II, which occurred in SAMP8 mice at 2 months of age and onwards. These proteins may serve as candidate biomarkers for early aging.

摘要

我们通过比较 2、6、12 和 15 月龄(SAMP8-2m、-6m、-12m、-15m)的快速老化小鼠(SAMP8)和年龄匹配的 SAM 抗性 1 型(SAMR1)小鼠的血清蛋白,评估了水平的变化。处死小鼠,通过二维电泳结合质谱分析血液。在所有 SAMP8 血清样本中均存在 5 个蛋白质斑点,但除了斑点 3 之外,仅在 15 月龄的 SAMR1 样本中出现,而斑点 3 在 SAMR1-12m 血清中也有轻微表达。在 SAMP8-2m、-6m 和-12m 小鼠的血清中,有 2 种蛋白质减少,并在 SAMP8-15m 血清中各自分为 2 个斑点。因此,SAMP8 血清中改变的斑点总数为 7;其中 4 种被鉴定为 Ig kappa 链 V 区(M-T413)、活性抑制 Fab 片段对细胞色素 P450 芳香酶的 A 链(32C2_A)、甲胎蛋白和载脂蛋白 A-II。M-T413 是一种单克隆 CD4 抗体,可抑制 T 细胞增殖。我们发现 SAMP8-2m 小鼠脾细胞中的 M-T413 RNA 水平显著增强。这与血清 M-T413 蛋白变化一致,并且 SAMP8 小鼠的血液 CD4+T 细胞计数明显低于年龄匹配的 SAMR1 小鼠,后者与血清 M-T413 蛋白体积呈负相关。血清蛋白的年龄相关性变化有利于自身抗体和甲胎蛋白的增加以及载脂蛋白 A-II 的减少,这种变化在 SAMP8 小鼠 2 月龄及以后发生。这些蛋白质可能成为早期衰老的候选生物标志物。

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