神经生长因子通过抑制 IRE1-JNK-CHOP 信号通路保护与内质网应激相关的视网膜神经节细胞。
Nerve Growth Factor Protects Retinal Ganglion Cells Related to Inhibiting Endoplasmic Reticulum Stress by Inhibiting IRE1-JNK-CHOP Signaling Pathway.
机构信息
Department of Pharmacy, The Eye Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
出版信息
Ocul Immunol Inflamm. 2022 Aug;30(6):1341-1346. doi: 10.1080/09273948.2021.1872651. Epub 2021 Apr 1.
BACKGROUND
Under various physiological conditions, endoplasmic reticulum stress can induce apoptotic cell death, leading to brain and retinal neuronal cell death, but the relations of ER stress-induced apoptosis and the nerve growth factor's therapeutic effect in Glaucoma optic neuropathy still unclear.
METHODS
An endoplasmic reticulum stress model was established in ganglion cells using TG, the endoplasmic reticulum stress inducer. MTT assay and flow cytometry were used to detect the protective effect of NGF on retinal ganglion cells. Western blot was used to detect apoptosis-related proteins Bcl-2, Bad and endoplasmic reticulum stress-related proteins GRP78, IRE1, JNK and CHOP.
RESULTS
MTT assay and flow cytometry showed NGF can protect the apoptosis of ganglion cells. Western blot analysis showed the level of pro-apoptotic protein Bad was decreased and anti-apoptotic protein Bcl-2 was increased after NGF treatment. Endoplasmic reticulum stress-induced proteins GRP78, IRE1, JNK and CHOP are counter- acted by NGF.
CONCLUSION
NGF protects retinal ganglion cells related to inhibiting endoplasmic reticulum stress by inhibiting IRE1-JNK-CHOP signaling pathway.
背景
在内质网各种生理条件下，内质网应激可诱导细胞凋亡，导致脑和视网膜神经元细胞死亡，但内质网应激诱导的凋亡与神经生长因子在青光眼视神经病变中的治疗效果的关系尚不清楚。
方法
使用内质网应激诱导剂 TG 在神经节细胞中建立内质网应激模型。MTT 检测和流式细胞术检测 NGF 对视网膜神经节细胞的保护作用。Western blot 检测凋亡相关蛋白 Bcl-2、Bad 和内质网应激相关蛋白 GRP78、IRE1、JNK 和 CHOP。
结果
MTT 检测和流式细胞术显示 NGF 可保护神经节细胞凋亡。Western blot 分析表明，NGF 处理后促凋亡蛋白 Bad 的水平降低，抗凋亡蛋白 Bcl-2 的水平升高。内质网应激诱导蛋白 GRP78、IRE1、JNK 和 CHOP 被 NGF 拮抗。
结论
NGF 通过抑制 IRE1-JNK-CHOP 信号通路抑制内质网应激，从而保护视网膜神经节细胞。
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