Expression of heat shock transcription factors and heat shock protein 72 in rat retina after intravitreal injection of low dose N-methyl-D-aspartate
Expression of heat shock transcription factors and heat shock protein 72 in rat retina after intravitreal injection of low dose N-methyl-D-aspartate
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DOI：
10.1016/j.neulet.2007.12.045
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发表时间：
2008-03-05
影响因子：
2.5
通讯作者：
Kwong, Jacky M. K.
中科院分区：
文献类型：
--
作者：
Ahn, Jaehong;Piri, Natik;Kwong, Jacky M. K.
热休克反应是细胞产生热休克蛋白（HSP）的遗传有序过程。各种压力源可以通过热休克转录因子（HSF）调节来触发反应。最近的研究表明，非致死水平的 N-甲基-D-天冬氨酸 (NMDA) 预处理具有神经保护作用，但确切机制尚不清楚。我们假设 NMDA 预处理的保护机制可能涉及 HSP 表达。为了了解压力下 HSP 的调节机制，我们检测了玻璃体内注射 NMDA 后成年大鼠视网膜中 Hsp72、HSF1 和 HSF2 的表达。逆行标记的视网膜神经节细胞 (RGC) 计数显示，玻璃体内 8 nmol（而非 0.8 nmol）NMDA 会降低 RGC 存活率。 Western blotting和免疫组织化学显示，非致死剂量（0.8 nmol）NMDA诱导HSF1和HSF2呈时间依赖性表达，并且RGC层中HSF1和HSF2的表达在注射后9至18 It之间达到峰值。与 HSF 表达增加平行，免疫组织化学和原位杂交表明，非致死性 NMDA 注射后 9 小时和 12 小时，Hsp72 mRNA 和蛋白表达分别增加。我们的研究结果表明 HSF1 和 HSF2 的表达与 Hsp72 相关的应激反应有关。 (c) 2008 Elsevier Ireland Ltd. 保留所有权利。
The heat shock response is a genetically well-ordered process for cell to generate heat shock protein (HSP). Various stressors can trigger the response through heat shock transcriptional factor (HSF) regulation. Recent studies demonstrated that preconditioning of N-methyl-D-aspartate (NMDA) at non-lethal levels has neuroprotective effects, but the exact mechanisms are unclear. We hypothesize that the protective mechanisms of NMDA preconditioning could involve HSP expression. To understand the regulatory mechanisms of HSP under stress, we examined the expression of Hsp72, HSF1 and HSF2 in the adult rat retina after intravitreal injection of NMDA. Retinal ganglion cell (RGC) counting with retrograde labeling showed that 8 nmol, but not 0.8 nmol, of intravitreal NMDA reduced RGC survival. Western blotting and immunohistochemistry showed that non-lethal (0.8 nmol) doses of NMDA induced a time-dependent expression of HSF1 and HSF2, and that the expression of HSF1 and HSF2 in the RGC layer peaked between 9 and 18 It after injection. Parallel to the increased HSF expression, immunohistochemistry and in situ hybridization demonstrated that Hsp72 mRNA and protein expression increased 9 and 12 h after non-lethal NMDA injection, respectively. Our findings suggest that the expression of HSF1 and HSF2 is associated with the Hsp72-related stress response. (c) 2008 Elsevier Ireland Ltd. All rights reserved.