title: Neuroprotection by GH against excitotoxic-induced cell death in retinal ganglion cells.
abstract: 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.
authors.affiliation: Department of Physiology, University of Alberta, Edmonton T6G 2H7, Canada.
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Martínez-Moreno
authors.affiliation: Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro, Qro. 76230, Mexico.
authors.forename: José
authors.initials: J
authors.lastname: Ávila-Mendoza
authors.affiliation: Department of Physiology, University of Alberta, Edmonton T6G 2H7, Canada.
authors.forename: Yilun
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro, Qro. 76230, Mexico.
authors.forename: Elvira Del Carmen
authors.initials: Edel C
authors.lastname: Arellanes-Licea
authors.affiliation: Department of Physiology, University of Alberta, Edmonton T6G 2H7, Canada.
authors.forename: Marcela
authors.initials: M
authors.lastname: Louie
authors.affiliation: Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro, Qro. 76230, Mexico.
authors.forename: Maricela
authors.initials: M
authors.lastname: Luna
authors.affiliation: Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro, Qro. 76230, Mexico.
authors.forename: Carlos
authors.initials: C
authors.lastname: Arámburo
authors.affiliation: Department of Physiology, University of Alberta, Edmonton T6G 2H7, Canada. Electronic address: steve.harvey@ualberta.ca.
authors.forename: Steve
authors.initials: S
authors.lastname: Harvey
mesh_terms: D000818:Animals; D017209:Apoptosis; D016923:Cell Death; D002645:Chickens; D013006:Growth Hormone / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D000066829:Neuroprotection; D012160:Retina / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone
keywords: Apoptosis; Buthionine sulfoxamide (BSO); Excitotoxicity; Glutamate; Growth hormone (GH); Insulin-like growth factor (IGF)-1