期刊
JOURNAL OF PHARMACOLOGICAL SCIENCES
卷 133, 期 1, 页码 34-41出版社
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1016/j.jphs.2016.12.002
关键词
Apelin; APJ; Knockout mouse; Neuroprotection; Retina
资金
- Center of Innovation Program from the Japan Science and Technology Agency (JST) [AS262Z00508Q]
- Japan Society for the Promotion of Science [JP15K07983]
- Setsunan University
- Grants-in-Aid for Scientific Research [15K07983] Funding Source: KAKEN
Glutamate excitotoxicity mediated by N-methyl-D-aspartate (NMDA) receptors is an important cause of retinal ganglion cell death in glaucoma. To elucidate whether apelin protects against retinal neuronal cell death, we examined protective effects of exogenous and endogenous apelin on neuronal cell death induced by intravitreal injection of NMDA in the retinas of mice. An intravitreal injection of NMDA induced neuronal cell death in both the retinal ganglion cell layer and inner nuclear layer, and reduced the amplitudes of scotopic threshold response (STR) in electroretinography studies. Both cell death and STR amplitudes decrease induced by NMDA were prevented by a co-injection of [Pyr(1)]-apelin-13, and were facilitated by apelin deficiency. The neuroprotective effects of [Pyr(1)]-apelin-13 were blocked by an apelin receptor APJ antagonist, and by inhibitors of Akt and extracellular signal-regulated kinase 1/2 signaling pathways. Additionally, an intravitreal injection of tumor necrosis factor-alpha (TNF-alpha) neutralizing antibody prevented NMDA-induced retinal neuronal cell death, and exogenous and endogenous apelin suppressed NMDA-induced upregulation of TNF-alpha in the retina. These results suggest that apelin protects neuronal cells against NMDA-induced death via an APJ receptor in the retina, and that apelin may have beneficial effects in the treatment of glaucoma. (C) 2017 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据