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Research Article

组蛋白去乙酰化酶6的抑制可保护海马细胞免受线粒体介导的严重缺氧-葡萄糖剥夺模型中的凋亡。

卷 19, 期 9, 2019

页: [673 - 682] 页: 10

弟呕挨: 10.2174/1566524019666190724102755

价格: $65

摘要

背景：组蛋白脱乙酰基酶（HDAC）6抑制剂已在创伤中显示出显着的保护作用。 但是，它们在神经保护作用和潜在机制中的作用了解甚少。 这项研究旨在调查HDAC6抑制剂Tubastatin A（Tub-A）在HT22海马细胞中的氧葡萄糖剥夺（OGD）期间的神经保护作用。 方法：将HT22海马细胞暴露于OGD。 通过细胞计数试剂盒8（CCK-8）和乳酸脱氢酶（LDH）释放测定法评估细胞活力和细胞毒性。 通过末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）测定法评估细胞凋亡。 使用JC-1染料检测线粒体膜电位。 通过蛋白质印迹分析来分析乙酰化的α-微管蛋白，α-微管蛋白，细胞色素c，VDAC，Bax，Bcl-2，切割的胱天蛋白酶3，磷酸化的Akt，Akt，磷酸化的GSK3β和GSK3β的表达。 结果：Tub-A诱导α-微管蛋白的乙酰化，证明适当的疗效。 暴露于OGD后，Tub-A显着增加了细胞活力并减弱了LDH的释放。 此外，Tub-A处理抑制了OGD后TUNEL阳性细胞的增加，并保留了线粒体膜电位。 Tub-A还减弱了细胞色素c从线粒体向细胞质的释放，并抑制了Bax / Bcl-2和裂解的半胱天冬酶3的比例。这部分是由Akt和GSK3β信号通路磷酸化的增加所介导的。 结论：使用Tub-A抑制HDAC 6可以通过调节Akt /GSK3β信号传导并抑制线粒体介导的凋亡来防止OGD诱导的HT22细胞损伤。

关键词: 组蛋白脱乙酰基酶6，氧葡萄糖剥夺，神经元，线粒体膜电位，凋亡，HT22细胞。

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