NYS Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
NYS Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA.
Life Sci. 2014 Mar 18;99(1-2):31-6. doi: 10.1016/j.lfs.2014.01.064. Epub 2014 Jan 28.
Gelsolin (GSN), a multifunctional protein, binds to amyloid beta-protein (Aβ), inhibits its fibrillization, solubilizes preformed Aβ fibrils, and helps in its clearance from the brain. Trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, induces the protein expression of gelsolin. In the present study, we investigated how TSA-treatment of APPswe/PS1δE9 transgenic (Tg) mice of Alzheimer's disease (AD) will affect the plasma levels of gelsolin and Aβ.
TSA (5mg/kg body weight on alternate days for two months) was intraperitoneally injected to AD Tg mice. Gelsolin was measured by Western blotting and Aβ was measured by enzyme-linked immunosorbent assay.
TSA-treatment significantly increased the levels of plasma gelsolin by 1.79-fold as compared with vehicle-treated control mice (p<0.01). The levels of Aβ 1-40 and Aβ 1-42 in the plasma were also higher in TSA-treated mice in comparison with vehicle-treated mice. The treatment of transgenic AD mice with TSA did not affect the body weight in both male and female groups as compared to vehicle-treated animals. A positive correlation was observed between the plasma levels of gelsolin and Aβ 1-40 (r=0.594, p=0.042) or Aβ 1-42 (r=0.616, p=0.033) in AD Tg mice.
These results suggest that TSA increases the levels of plasma gelsolin and Aβ in AD Tg mice, which may have implications in gelsolin-mediated clearance of Aβ.
凝溶胶蛋白（GSN）是一种多功能蛋白，能与淀粉样β蛋白（Aβ）结合，抑制其纤维形成，溶解已形成的 Aβ 纤维，并有助于其从大脑中清除。曲古抑菌素 A（TSA）是一种组蛋白去乙酰化酶（HDAC）抑制剂，能诱导 GSN 的蛋白表达。在本研究中，我们研究了 TSA 处理阿尔茨海默病（AD）的 APPswe/PS1δE9 转基因（Tg）小鼠会如何影响 GSN 和 Aβ 的血浆水平。
AD Tg 小鼠腹腔内注射 TSA（5mg/kg 体重，隔日一次，共两个月）。通过 Western blot 测定 GSN，通过酶联免疫吸附试验测定 Aβ。
与对照组相比，TSA 处理使血浆 GSN 水平显著增加了 1.79 倍（p<0.01）。与对照组相比，TSA 处理组小鼠的血浆 Aβ 1-40 和 Aβ 1-42 水平也更高。与对照组相比，TSA 处理对雄性和雌性 AD Tg 小鼠的体重均无影响。在 AD Tg 小鼠中，GSN 与 Aβ 1-40（r=0.594，p=0.042）或 Aβ 1-42（r=0.616，p=0.033）的血浆水平呈正相关。
这些结果表明，TSA 增加了 AD Tg 小鼠的血浆 GSN 和 Aβ 水平，这可能对 GSN 介导的 Aβ 清除有影响。
