中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (11): 1945-1952.doi: 10.4103/1673-5374.239443

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

大鼠损伤脊髓胶质纤维酸性蛋白与组蛋白H4乙酰化水平相关

  

  • 收稿日期:2018-08-02 出版日期:2018-11-15 发布日期:2018-11-15
  • 基金资助:

    该研究得到了巴西资助机构CNPq，CAPES和FAPERGS的支持

Glial fibrillary acidic protein levels are associated with global histone H4 acetylation after spinal cord injury in rats

Mayara Ferraz de Menezes1, 2, Fabrício Nicola3, Ivy Reichert Vital da Silva4, Adriana Vizuete3, Viviane Rostirola Elsner4, Léder Leal Xavier1, 2, Carlos Alberto Saraiva Gonçalves3, Carlos Alexandre Netto3, Régis Gemerasca Mestriner1, 2   

  1. 1 Neurorehabilitation and Neural Repair Research Group, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil
    2 Graduate Program in Cellular and Molecular Biology, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil
    3 Department of Biochemistry, Basic Science Institute, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
    4 Graduate Program in Biosciences and Rehabilitation. Centro Universitário Metodista IPA, Porto Alegre, RS, Brazil
  • Received:2018-08-02 Online:2018-11-15 Published:2018-11-15
  • Contact: Viviane Rostirola Elsner, PhD,elsner.viviane@gmail.com.
  • Supported by:

    This research was supported by Brazilian funding agencies CNPq, CAPES and FAPERGS.

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摘要：

现有证据表明，组蛋白H4乙酰化状态在神经可塑性中起着重要作用。星形细胞反应性影响SCI后的组织重塑。然而，脊髓损伤（SCI）后组蛋白H4乙酰化与星形细胞反应性间的联系仍然知之甚少。为探讨胶质纤维酸性蛋白（GFAP）和S100钙结合蛋白B（S100B）（星形细胞反应性标志物）和组蛋白H4乙酰化水平之间的关系。实验将成年雄性Wistar大鼠随机分为6组：假手术组和脊髓损伤后6，24，48，72h和7d组。结果表明，胶质纤维酸性蛋白而非S100B与组蛋白H4乙酰化水平相关。同时，组蛋白H4乙酰化水平在脊髓损伤后表现出复杂的模式，至少包括3个明确定义的阶段：第1阶段–伤后6,24和48 h无变化;第2阶段：伤后72h水平增加;以及第3阶段 – 伤后7d内恢复到与假手术组相似的水平）。这些结果表明组蛋白H4乙酰化水平在脊髓损伤后第一周表现出不同的表达模式，这可能与病灶周围组织中的胶质纤维酸性蛋白水平有关。目前的数据支持使用H4乙酰化作为脊髓损伤后组织重塑的潜在生物标志物。

orcid:0000-0003-4158-181X(Viviane Rostirola Elsner)

 

关键词: 组蛋白, 脊髓损伤, 胶质纤维酸性蛋白, S100钙结合蛋白B, 星形胶质细胞, 神经可塑性, ELISA, 神经修复, 大鼠

Abstract:

Emerging evidence has suggested global histone H4 acetylation status plays an important role in neural plasticity. For instance, the imbalance of this epigenetic marker has been hypothesized as a key factor for the development and progression of several neurological diseases. Likewise, astrocytic reactivity - a wellknown process that markedly influences the tissue remodeling after a central nervous system injury - is crucial for tissue remodeling after spinal cord injury (SCI). However, the linkage between the above-mentioned mechanisms after SCI remains poorly understood. We sought to investigate the relation between both glial fibrillary acidic protein (GFAP) and S100 calcium-binding protein B (S100B) (astrocytic reactivity classical markers) and global histone H4 acetylation levels. Sixty-one male Wistar rats (aged ~3 months) were divided into the following groups: sham; 6 hours post-SCI; 24 hours post-SCI; 48 hours post-SCI; 72 hours post-SCI; and 7 days post-SCI. The results suggested that GFAP, but not S100B was associated with global histone H4 acetylation levels. Moreover, global histone H4 acetylation levels exhibited a complex pattern after SCI, encompassing at least three clearly defined phases (first phase: no changes in the 6, 24 and 48 hours post-SCI groups; second phase: increased levels in the 72 hours post-SCI group; and a third phase: return to levels similar to control in the 7 days post-SCI group). Overall, these findings suggest global H4 acetylation levels exhibit distinct patterns of expression during the first week post-SCI, which may be associated with GFAP levels in the perilesional tissue. Current data encourage studies using H4 acetylation as a possible biomarker for tissue remodeling after spinal cord injury.

Key words: histones, spinal cord injury, glial fibrillary acidic protein, S100 calcium-binding protein B, neural plasticity, astrocyte, ELISA-immunoassay, recovery, neural repair, rats