Involvement of transcription factors in apoptosis of the Retinal Ganglion Cells by Optic Nerve Transection.

转录因子参与视神经横断引起的视网膜神经节细胞凋亡。

• 批准号: 14571651
• 负责人: YOSHIDA Kazuhiko
• 金额: $ 1.92万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571651/
• 关键词: c-Jun; phosphorylation; retina; optic nerve; apoptosis; knock-in mouse; TUNEL staining; immunocytochemistry

To examine the involvement of c-Jun and c-Jun N-terminal phosphorylation (JNP) in apoptosis of retinal ganglion cells (RGCs) after the optic nerve (ON) transection, the expression and phosphorylation of c-Jun protein and apoptosis in RGCs were examined after ON transection in wild-type mice and mice in which both phosphoacceptor serines of Jun have mutated to alanines (c-Jun[AA] mice). The fluorescent tracer 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) was applied to the superior colliculi (SC), and the right ON was severed after 7 days. After two more weeks, the average number of RGCs per field was calculated. JNP and TUNEL-labeled apoptotic nuclei were detected in the ganglion cell layer (GCL) of the retina of the wild-type mice in response to ON transection. The numbers of TUNEL-positive nuclei in the c-Jun(AA) mice was reduced in comparison to those in wild-type mice. Retrograde labeling showed that the number of the RGCs in the retinas on the injured side of the c-Jun(AA) mice was significantly higher than in wild-type mice 14 days after the lesion. These results suggest that there is a partial but significant contribution of JNP to the induction of apoptosis m RGCs by ON transaction.

目的探讨c-Jun和c-Jun氨基末端磷酸化(JNP)在视神经(ON)横断后视网膜神经节细胞(RGC)凋亡中的作用，以及c-Jun蛋白的表达和磷酸化以及RGC细胞凋亡。在野生型小鼠和 Jun 的两个磷酸受体丝氨酸突变为丙氨酸的小鼠（c-Jun[AA] 小鼠）中进行 ON 横断后检查。将荧光示踪剂1,1'-双十八烷基-3,3,3',3'-四甲基吲哚羰花青高氯酸盐(DiI)应用于上丘(SC)，7天后切断右侧ON。再过两周后，计算每个视野的平均 RGC 数量。在野生型小鼠视网膜神经节细胞层 (GCL) 中检测到 ON 横断反应中的 JNP 和 TUNEL 标记的凋亡细胞核。与野生型小鼠相比，c-Jun(AA)小鼠中TUNEL阳性细胞核的数量减少。逆行标记显示，损伤后14天，c-Jun(AA)小鼠损伤侧视网膜中的RGC数量明显高于野生型小鼠。这些结果表明，JNP 对通过 ON 事务诱导 RGC 凋亡有部分但显着的贡献。

项目成果

Ohgami K, Ilieva IB, Shiratori K, Isogai E, Yoshida K, Kotake S, Nishida T, Mizuki N, Ohno S.: "Effect of human cationic antimicrobial protein 18 Peptide on endotoxin-induced uveitis in rats."Invest Ophthalmol Vis Sci.. 44. 4412-4418 (2003)

Ohgami K、Ilieva IB、Shiratori K、Isogai E、Yoshida K、Kotake S、Nishida T、Mizuki N、Ohno S.：“人阳离子抗菌蛋白 18 肽对大鼠内毒素诱导的葡萄膜炎的影响。”Invest Ophasemol Vis Sci

Imaki J, et al.: "Developmental expression of mafB messenger ribonucleic acids in rat skin by in situ hybridization histochemistry."J Dermatol Sci.. 33・2. 134-136 (2003)

Imaki J 等：“通过原位杂交组织化学研究大鼠皮肤中 mafB 信使核糖核酸的发育表达。”J Dermatol Sci.. 134-136 (2003)。

Shiratori K, et al.: "Inhibition of endotoxin-induced uveitis and potentiation of cyclooxygenase-2 protein expression by alpha-melanocyte-stimulating hormone."Invest Ohthalmol Vis Sci.. 45・1. 159-164 (2004)

Shiratori K 等人：“α-黑素细胞刺激激素对内毒素诱导的葡萄膜炎的抑制和环氧合酶 2 蛋白表达的增强”。Invest Ohthalmol Vis Sci.. 159-164 (2004)。

Imaki J, Onodera H, Mishima T, Yoshida K, Sakai M.: "Developmental expression of mafB messenger ribonucleic acids in rat skin by in situ hybridization histochemistry."J Dennatol Sci.. 33(2). 134-136 (2003)

Imaki J、Onodera H、Mishima T、Yoshida K、Sakai M.：“通过原位杂交组织化学研究大鼠皮肤中 mafB 信使核糖核酸的发育表达。”J Dennatol Sci.. 33(2)。

Harada C, Harada T, Quah HM, Maekawa F, Yoshida K, Ohno S, Wada K, Parada LF, Tanaka K.: "Potential role of glial cell line-derived neurotrophic factor receptors in Muller glial cells during light-induced retinal degeneration."Neuroscience. 122(1). 229-23

Harada C、Harada T、Quah HM、Maekawa F、Yoshida K、Ohno S、Wada K、Parada LF、Tanaka K.：“胶质细胞系源性神经营养因子受体在光诱导视网膜变性过程中 Muller 胶质细胞中的潜在作用