视神经损伤后JNK3、APP蛋白的表达变化对视网膜神经节细胞存活的影响
The Expression Changes of JNK3 and APP Protein in Apoptosis of Retinal Ganglion Cells after Optic Nerve Injury
-
摘要: 目的 探讨视神经损伤后小鼠视网膜神经节细胞 (RGCs) 中JNK3、APP蛋白的表达变化及其对RGCs存活的影响.方法 取成年APP野生型小鼠, 采用钳夹法建立视神经损伤模型, 应用免疫组织化学、Western blot法检测造模后视网膜神经节细胞中JNK3、APP蛋白的定位和定量表达变化, 比较损伤7 d后APP基因敲除组及其同窝野生型小鼠RGCs的存活数变化.结果 视神经损伤后, 视网膜神经节细胞中JNK3定位于细胞浆, p-JNK则从细胞浆进入到细胞核中表达, APP定位于细胞膜、p-APP在轴突及细胞浆中均表达.同时, Western结果表明上述4种蛋白表达量在损伤1 d组比假手术组均升高 (P<0.01) .与APP野生型小鼠视网膜神经节细胞存活数 (127.7±7.0) 相比, APP基因敲除组小鼠视网膜神经节细胞存活数 (147±7.0) 明显增多 (P<0.05) .结论 视神经损伤后, JNK3、APP蛋白的表达增多在视网膜神经节细胞的存活中发挥了一定的作用.Abstract: Objective To investigate the changes in the expression of JNK3 and APP protein in retinal ganglion cells (RGCs) after optic nerve injury and its effect on the survival of RGCs. Me thods Optic nerve crush models were established using adult APP wild type mice. Immunohistochemistry and western blot for detecting the expression of JNK3 and APP protein in RGCs were used post-injury. The number of RGCs in APP KO mice group was counted to compare with APP WT mice group. Re s ults After optic nerve injury, JNK3 expressed in cytoplasm of RGCs; p-JNK transformed from cytoplasm to nuclei of RGCs; APP expressed in cytomembrane; p-APP expressed in cytoplasm and axons of RGCs. Western blot results showed that the protein expressions of JNK3, p-JNK, APP and p-APP were increased in the injured group (P<0.01) . The survival number of RGCs (147±7.0) in APP KO mice group increased significantly than APP WT mice group (127.7 ±7.0) (P <<0.05) .Conclus ion The upregulation of JNK3 and APP protein expression maybe play an important role in RGCs survival proceeds after optic nerve injury.
-
Key words:
- JNK3 /
- Amyloid precursor protein /
- Retinal ganglion cells
-
[1] [1]MINDEN A, KARIN M.Regulation and function of the JNK subgroup of MAP kinases[J].Biochim Biophys Acta, 1997, 1333 (2) :F85-104. [2] [2] GUPTA S, BARRETT T, WHITMARSH J J, et al.Selective interaction of JNK protein kinase isoforms with transcription factors[J].EMBO J, 1996, 15 (11) :2760-2770. [3] [3] KUAN C Y, WHITMARSH A J, YANG D D, et al.A criticalrole of neural-specific JNK3 for ischemic apoptosis[J].Proc Natl Acad Sci U S A, 2003, 100 (25) :15184-15189. [4] [4] LIU C, TAN F C, XIAO Z C, et al.Amyloid precursor protein enhances Nav1.6 sodium channel cell surface expression[J].J Biol Chem, 2015, 290 (19) :12048-12057. [5] [5] YAGHMAEI P, AZARFAR K, DEZFULIAN M, et al.Silymarin effect on amyloid-beta plaque accumulation and gene expression of APP in an Alzheimer's disease rat model[J].Daru, 2014, 22 (1) :24. [6] [6] TAMAS A, ZSOMBOK A, FARKAS O, et al., Postinjury administration of pituitary adenylate cyclase activating polypeptide (PACAP) attenuates traumatically induced axonal injury in rats[J].J Neurotrauma, 2006, 23 (5) :686-695. [7] [7]ZHENG H, JIANG M, TRUMBAUER M E, et al.beta-Amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity[J].Cell, 1995, 81 (4) :525-531. [8] [8]BESSERO A C, CHIODINI F, RUNGGER-BRANDLE E, et al.Role of the c-Jun N-terminal kinase pathway in retinal excitotoxicity, and neuroprotection by its inhibition[J].J Neurochem, 2010, 113 (5) :1307-1318. [9] [9] SUN H, WANG T, PANG I H, et al.rotective effect of a JNK inhibitor against retinal ganglion cell loss induced by acute moderate ocular hypertension[J].Mol Vis, 2011, 17:864-875. [10] [10] LV B, HUO F, DANG X, et al.Puerarin Attenuates N-Methyl-D-aspartic acid-induced apoptosis and retinal ganglion cell damage through the JNK/p38 MAPK pathway[J].J Glaucoma, 2016, 25 (9) :e792-801. [11] [11]BOGOYEVITCH MA.The isoform-specific functions of the c-Jun N-terminal Kinases (JNKs) :differences revealed by gene targeting[J].Bioessays, 2006, 28 (9) :923-934. [12] [12] EGAWA N, WANG Q, GRIFFIN H M, et al.HPV16 and18 genome amplification show different E4-dependence, with 16E4 enhancing E1 nuclear accumulation and replicative efficiency via its cell cycle arrest and kinase activation functions[J].PLo S Pathog, 2017, 13 (3) :e1006282. [13] [13]HENLEY J, POO MM, Guiding neuronal growth cones using Ca2+signals[J].Trends Cell Biol, 2004, 14 (6) :320-330. [14] [14]HE Y, CHEN J, ZHANG S G, et al.c-Jun N-terminal kinase 3 expression in the retina of ocular hypertension mice:a possible target to reduce ganglion cell apoptosis[J].Neural Regen Res, 2015, 10 (3) :432-437. [15] [15]KIM G H, LEE J J, LEE S H, et al.Exposure of isoflurane-treated cells to hyperoxia decreases cell viability and activates the mitochondrial apoptotic pathway[J].Brain Res, 2016, 1636:13-20. [16] [16] MCKINNON S J, LEHMAN D M, KERRIGAN-BAUMRIND L A, et al.Caspase activation and amyloid precursor protein cleavage in rat ocular hypertension[J].Invest Ophthalmol Vis Sci, 2002, 43 (4) :1077-1087.
点击查看大图
计量
- 文章访问数: 1543
- HTML全文浏览量: 568
- PDF下载量: 58
- 被引次数: 0