PMID- 23978538 OWN - NLM STAT- MEDLINE DCOM- 20140530 LR - 20201209 IS - 1873-2747 (Electronic) IS - 0361-9230 (Linking) VI - 98 DP - 2013 Sep TI - RTP801 immunoreactivity in retinal ganglion cells and its down-regulation in cultured cells protect them from light and cobalt chloride. PG - 132-44 LID - S0361-9230(13)00136-6 [pii] LID - 10.1016/j.brainresbull.2013.08.002 [doi] AB - 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 (10muM). 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. CI - Copyright (c) 2013 Elsevier Inc. All rights reserved. FAU - del Olmo-Aguado, Susana AU - del Olmo-Aguado S AD - Fundacion de Investigacion Oftalmologica, Avda. Doctores Fernandez-Vega 34, E-33012 Oviedo, Asturias, Spain. FAU - Nunez-Alvarez, Claudia AU - Nunez-Alvarez C FAU - Ji, Dan AU - Ji D FAU - Manso, Alberto Garcia AU - Manso AG FAU - Osborne, Neville N AU - Osborne NN LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130824 PL - United States TA - Brain Res Bull JT - Brain research bulletin JID - 7605818 RN - 0 (Antimutagenic Agents) RN - 0 (Ddit4 protein, rat) RN - 0 (Immunosuppressive Agents) RN - 0 (Proton Ionophores) RN - 0 (Reactive Oxygen Species) RN - 0 (Repressor Proteins) RN - 0 (Transcription Factors) RN - 3G0H8C9362 (Cobalt) RN - 555-60-2 (Carbonyl Cyanide m-Chlorophenyl Hydrazone) RN - EVS87XF13W (cobaltous chloride) SB - IM MH - Animals MH - Antimutagenic Agents/*pharmacology MH - Apoptosis/drug effects/radiation effects MH - Carbonyl Cyanide m-Chlorophenyl Hydrazone/pharmacology MH - Cell Line, Transformed MH - Cobalt/*pharmacology MH - Dose-Response Relationship, Drug MH - Down-Regulation/*drug effects MH - Humans MH - Immunosuppressive Agents/pharmacology MH - Kidney/drug effects/metabolism MH - *Light MH - Mice MH - Proton Ionophores/pharmacology MH - Rats MH - Rats, Wistar MH - Reactive Oxygen Species/metabolism MH - Repressor Proteins/genetics/*metabolism MH - Retina/cytology MH - *Retinal Ganglion Cells/drug effects/metabolism/radiation effects/ultrastructure MH - Transcription Factors OTO - NOTNLM OT - Blue light OT - Chemical hypoxia OT - Ganglion cells OT - Neuroprotection OT - RTP801 OT - Rapamycin EDAT- 2013/08/28 06:00 MHDA- 2014/05/31 06:00 CRDT- 2013/08/28 06:00 PHST- 2013/06/25 00:00 [received] PHST- 2013/08/13 00:00 [revised] PHST- 2013/08/14 00:00 [accepted] PHST- 2013/08/28 06:00 [entrez] PHST- 2013/08/28 06:00 [pubmed] PHST- 2014/05/31 06:00 [medline] AID - S0361-9230(13)00136-6 [pii] AID - 10.1016/j.brainresbull.2013.08.002 [doi] PST - ppublish SO - Brain Res Bull. 2013 Sep;98:132-44. doi: 10.1016/j.brainresbull.2013.08.002. Epub 2013 Aug 24.