title: Nogo/RTN4 isoforms and RTN3 expression protect SH-SY5Y cells against multiple death insults.
abstract: Among the members of the reticulon (RTN) family, Nogo-A/RTN4A, a prominent myelin-associated neurite growth inhibitory protein, and RTN3 are highly expressed in neurons. However, neuronal cell-autonomous functions of Nogo-A, as well as other members of the RTN family, are unclear. We show here that SH-SY5Y neuroblastoma cells stably over-expressing either two of the three major isoforms of Nogo/RTN4 (Nogo-A and Nogo-B) or a major isoform of RTN3 were protected against cell death induced by a battery of apoptosis-inducing agents (including serum deprivation, staurosporine, etoposide, and H2O2) compared to vector-transfected control cells. Nogo-A, -B, and RTN3 are particularly effective in terms of protection against H2O2-induced increase in intracellular reactive oxygen species levels and ensuing apoptotic and autophagic cell death. Expression of these RTNs upregulated basal levels of Bax, activated Bax, and activated caspase 3, but did not exhibit an enhanced ER stress response. The protective effect of RTNs is also not dependent on classical survival-promoting signaling pathways such as Akt and Erk kinase pathways. Neuron-enriched Nogo-A/Rtn4A and RTN3 may, therefore, exert a protective effect on neuronal cells against death stimuli, and elevation of their levels during injury may have a cell-autonomous survival-promoting function.
authors: Department of Biochemistry, National University of Singapore, MD7, 8 Medical Drive, Singapore, 117597, Republic of Singapore.
authors: Felicia Yu Hsuan
authors: FY
authors: Teng
authors: Bor Luen
authors: BL
authors: Tang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics*; D002070:Butadienes / Q000494:pharmacology; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology; D059865:Endoplasmic Reticulum Stress; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D059565:G2 Phase Cell Cycle Checkpoints; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D000070798:Nogo Proteins; D016877:Oxidants / Q000494:pharmacology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002070:Butadienes; D002352:Carrier Proteins; D002867:Chromones; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D009025:Morpholines; D009185:Myelin Proteins; D009419:Nerve Tissue Proteins; D009570:Nitriles; D000070798:Nogo Proteins; D016877:Oxidants; D020033:Protein Isoforms; C476198:RTN3 protein, human; C000603199:RTN4 protein, human; C113580:U 0126; D051028:bcl-2-Associated X Protein; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D005047:Etoposide; D006861:Hydrogen Peroxide; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3; D019311:Staurosporine
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