Involvement of Fra-1 in Retinal Ganglion Cell Apoptosis in Rat Light-Induced Retina Damage Model
Involvement of Fra-1 in Retinal Ganglion Cell Apoptosis in Rat Light-Induced Retina Damage Model
复制标题
Fra-1参与大鼠光致视网膜损伤模型视网膜神经节细胞凋亡
DOI：
10.1007/s10571-016-0346-3
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发表时间：
2017-01-01
影响因子：
4
通讯作者：
Chen, Hui
中科院分区：
文献类型：
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作者：
Liu, Xiaojuan;Yang, Xiaowei;Chen, Hui
细胞周期重入是神经元凋亡的关键过程，其中转录因子FOS相关抗原1（Fra-1）起重要作用。然而，Fra-1在视网膜神经节细胞（RGC）凋亡中的表达和功能尚不清楚。为了研究Fra-1是否参与RGC凋亡，我们在成年大鼠中进行了光诱导的视网膜损伤模型。Western blot结果显示，光照后视网膜Fra-1表达上调。免疫组化显示，LE后Fra-1主要表达于视网膜神经节细胞层（GCL）的RGC。同时检测到LE后GCL中Fra-1与活性caspase-3或TUNEL阳性细胞的共定位。此外，LE后视网膜中Fra-1的表达与细胞周期蛋白D1和磷酸化丝裂原活化蛋白激酶p38（p-p38）的表达平行增加。此外，玻璃体内注射SB 203580，一种高度选择性的p38 MAP激酶（p38 MAPK）抑制剂，可降低Fra-1，cyclin D1和活性caspase-3蛋白的表达。提示Fra-1可能通过细胞周期重入机制参与了p38 MAPK调控的LE后RGC凋亡。
Cell cycle re-entry, in which Fra-1 (transcription factor FOS-related antigen 1) plays an important role, is a key process in neuronal apoptosis. However, the expression and function of Fra-1 in retinal ganglion cell (RGC) apoptosis are unknown. To investigate whether Fra-1 was involved in RGC apoptosis, we performed a light-induced retinal damage model in adult rats. Western blot revealed that up-regulation of Fra-1 expression appeared in retina after light exposure (LE). Immunostaining indicated that increased Fra-1 was mainly expressed in RGCs in retinal ganglion cell layer (GCL) after LE. Co-localization of Fra-1 with active caspase-3 or TUNEL-positive cells in GCL after LE was also detected. In addition, Fra-1 expression increased in parallel with cyclin D1 and phosphorylated mitogen-activated protein kinase p38 (p-p38) expression in retina after LE. Furthermore, Fra-1, cyclin D1, and active caspase-3 protein expression decreased by intravitreal injection of SB203580, a highly selective inhibitor of p38 MAP kinase (p38 MAPK). All these results suggested that Fra-1 may be associated with RGC apoptosis after LE regulated by p38 MAPK through cell cycle re-entry mechanism.