title: RTP801 immunoreactivity in retinal ganglion cells and its down-regulation in cultured cells protect them from light and cobalt chloride.
abstract: RTP801, a stress-related protein, is activated by adverse environmental conditions and inhibits the activity of mammalian target of rapamycin (mTOR) in promoting oxidative stress-dependent cell death. RTP801 exists both in the mammalian retina and the lens of the eye. Here, we observed RTP801 immunoreactivity in some retinal ganglion cells. Intravitreal injection of cobalt chloride (CoCl2) to mimick hypoxia influenced retinal GFAP (glial fibrillary acidic protein) and heme oxygenase-1 (HO-1) levels, but did not affect RTP801 immunoreactivity or mRNA content relative to GAPDH. However, RTP801 mRNA was elevated when compared with Brn3a mRNA, suggesting that RTP801 is activated in stressed Brn3a retinal ganglion cells. In cultures of RGC-5 cells, RTP801 immunoreactivity was located in the cytoplasm and partly present in the mitochondria. An insult of blue light or CoCl2 increased RTP801 expression, which was accompanied by cell death. However, in cultures where RTP801 mRNA was down-regulated, the negative influence of blue light and CoCl2 was blunted. Rapamycin nullified the CoCl2-induced up-regulation of RTP801 and attenuated cell death. Moreover, rapamycin was non-toxic to RGC-5 cells, even at a high concentration (10μM). The protective effect of rapamycin on RGC-5 cells caused by the inhibition of RTP801 suggests that rapamycin might attenuate retinal ganglion cell death in situ, as in glaucoma.
authors: Fundación de Investigación Oftalmológica, Avda. Doctores Fernández-Vega 34, E-33012 Oviedo, Asturias, Spain.
authors: Susana
authors: S
authors: del Olmo-Aguado
authors: Claudia
authors: C
authors: Núñez-Álvarez
authors: Dan
authors: D
authors: Ji
authors: Alberto García
authors: AG
authors: Manso
authors: Neville N
authors: NN
authors: Osborne
mesh_terms: D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002461:Cell Line, Transformed; D003035:Cobalt / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008027:Light; D051379:Mice; D061209:Proton Ionophores / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000166:cytology; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects / Q000648:ultrastructure; D014157:Transcription Factors
chemical_list: D016587:Antimutagenic Agents; C000632146:Ddit4 protein, rat; D007166:Immunosuppressive Agents; D061209:Proton Ionophores; D017382:Reactive Oxygen Species; D012097:Repressor Proteins; D014157:Transcription Factors; D003035:Cobalt; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; C018021:cobaltous chloride
keywords: Blue light; Chemical hypoxia; Ganglion cells; Neuroprotection; RTP801; Rapamycin