Neuroprotection by GH against excitotoxic-induced cell death in retinal ganglion cells

被引:21
作者
Martinez-Moreno, Carlos G. [1 ]
Avila-Mendoza, Jose [2 ]
Wu, Yilun [1 ]
del Carmen Arellanes-Licea, Elvira [2 ]
Louie, Marcela [1 ]
Luna, Maricela [2 ]
Aramburo, Carlos [2 ]
Harvey, Steve [1 ]
机构
[1] Univ Alberta, Dept Physiol, 7-41 Med Sci Bldg, Edmonton, AB T6G 2H7, Canada
[2] Univ Nacl Autonoma Mexico, Inst Neurobiol, Dept Neurobiol Celular & Mol, Campus Juriquilla, Queretaro 76230, Qro, Mexico
基金
加拿大自然科学与工程研究理事会;
关键词
Growth hormone (GH); Insulin-like growth factor (IGF)-1; Glutamate; Buthionine sulfoxamide (BSO); Excitotoxicity; Apoptosis; GROWTH-HORMONE GH; METHYL-D-ASPARTATE; CHICK-EMBRYO; NEURAL RETINA; EXPERIMENTAL GLAUCOMA; SIGNALING MECHANISMS; INTRAOCULAR-PRESSURE; HYPOXIA-ISCHEMIA; VISUAL-SYSTEM; GLUTAMATE;
D O I
10.1016/j.ygcen.2016.03.023
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Retinal growth hormone (GH) has been shown to promote cell survival in retinal ganglion cells (RGCs) during developmental waves of apoptosis during chicken embryonic development. The possibility that it might also against excitotoxicity-induced cell death was therefore examined in the present study, which utilized quail-derived QNR/D cells as an in vitro RGC model. QNR/D cell death was induced by glutamate in the presence of BSO (buthionine sulfoxamide) (an enhancer of oxidative stress), but this was significantly reduced (P < 0.01) in the presence of exogenous recombinant chicken GH (rcGH). Similarly, QNR/D cells that had been prior transfected with a GH plasmid to overexpress secreted and non-secreted GH. This treatment reduced the number of TUNEL-labeled cells and blocked their release of lactate dehydrogenase (LDH). In a further experiment with dissected neuroretinal explants from ED (embryonic day) 10 embryos, rcGH treatment of the explants also reduced (P < 0.01) the number of glutamate-BSO-induced apoptotic cells and blocked the explant release of LDH. This neuroprotective action was likely mediated by increased STAT5 phosphorylation and increased bcl-2 production, as induced by exogenous rcGH treatment and the media from GH-overexpressing QNR/D cells. As rcGH treatment and GH-overexpression cells also increased the content of IGF-1 and IGF-1 mRNA this neuroprotective action of GH is likely to be mediated, at least partially, through an IGF-1 mechanism. This possibility is supported by the fact that the siRNA knockdown of GH or IGF-1 significantly reduced QNR/D cell viability, as did the immunoneutralization of IGF-1. GH is therefore neuroprotective against excitotoxicity-induced RGC cell death by anti-apoptotic actions involving IGF-1 stimulation. (C) 2016 Elsevier Inc. All rights reserved.
引用
收藏
页码:68 / 80
页数:13
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