{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T05:30:06Z","timestamp":1773725406856,"version":"3.50.1"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2015,11,5]],"date-time":"2015-11-05T00:00:00Z","timestamp":1446681600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["ID0EOEAE1949"],"award-info":[{"award-number":["ID0EOEAE1949"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["ID0ESFAE1950"],"award-info":[{"award-number":["ID0ESFAE1950"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Neurobiol"],"published-print":{"date-parts":[[2016,11]]},"DOI":"10.1007\/s12035-015-9506-6","type":"journal-article","created":{"date-parts":[[2015,11,5]],"date-time":"2015-11-05T01:38:34Z","timestamp":1446687514000},"page":"6124-6135","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["NRF2 Mediates Neuroblastoma Proliferation and Resistance to Retinoic Acid Cytotoxicity in a Model of In Vitro Neuronal Differentiation"],"prefix":"10.1007","volume":"53","author":[{"given":"Vitor","family":"de Miranda Ramos","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfeu","family":"Zanotto-Filho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matheus Augusto","family":"de Bittencourt Pasquali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karina","family":"Klafke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juciano","family":"Gasparotto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Dunkley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel Pens","family":"Gelain","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Cl\u00e1udio Fonseca","family":"Moreira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2015,11,5]]},"reference":[{"key":"9506_CR1","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1002\/dvg.20444","volume":"46","author":"F Campo-Paysaa","year":"2008","unstructured":"Campo-Paysaa F, Marl\u00e9taz F, Laudet V, Schubert M (2008) Retinoic acid signaling in development: tissue-specific functions and evolutionary origins. Genesis 46:640\u2013656","journal-title":"Genesis"},{"key":"9506_CR2","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/j.cell.2008.09.002","volume":"134","author":"G Duester","year":"2008","unstructured":"Duester G (2008) Retinoic acid synthesis and signaling during early organogenesis. Cell 134:921\u2013931","journal-title":"Cell"},{"key":"9506_CR3","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/nrn963","volume":"3","author":"M Maden","year":"2002","unstructured":"Maden M (2002) Retinoid signalling in the development of the central nervous system. Nat Rev Neurosci 3:843\u2013853","journal-title":"Nat Rev Neurosci"},{"key":"9506_CR4","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/S0304-3835(03)00108-3","volume":"197","author":"CP Reynolds","year":"2003","unstructured":"Reynolds CP, Matthay KK, Villablanca JG, Maurer BJ (2003) Retinoid therapy of high-risk neuroblastoma. Cancer Lett 197:185\u2013192","journal-title":"Cancer Lett"},{"key":"9506_CR5","first-page":"1","volume":"00","author":"J Ablain","year":"2014","unstructured":"Ablain J, de Th\u00e9 H (2014) Retinoic acid signaling in cancer: the parable of acute promyelocytic leukemia. Int J Cancer 00:1\u201311","journal-title":"Int J Cancer"},{"key":"9506_CR6","first-page":"589","volume":"68","author":"N Sidell","year":"1982","unstructured":"Sidell N (1982) Retinoic acid-induced growth inhibition and morphologic differentiation of human neuroblastoma cells in vitro. J Natl Cancer Inst 68:589\u2013596","journal-title":"J Natl Cancer Inst"},{"key":"9506_CR7","doi-asserted-by":"crossref","first-page":"4721","DOI":"10.1242\/jcs.02603","volume":"118","author":"JC Liou","year":"2005","unstructured":"Liou JC, Ho SY, Shen MR, Liao YP, Chiu WT, Kang KH (2005) A rapid, nongenomic pathway facilitates the synaptic transmission induced by retinoic acid at the developing synapse. J Cell Sci 118:4721\u20134730","journal-title":"J Cell Sci"},{"key":"9506_CR8","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1046\/j.1471-4159.2000.0750991.x","volume":"75","author":"M Encinas","year":"2000","unstructured":"Encinas M, Iglesias M, Liu Y, Wang H, Muhaisen A, Ce\u00f1a V, Gallego C, Comella JX (2000) Sequential treatment of SH-SY5Y cells with retinoic acid and brain-derived neurotrophic factor gives rise to fully differentiated, neurotrophic factor-dependent, human neuron-like cells. J Neurochem 75:991\u20131003","journal-title":"J Neurochem"},{"key":"9506_CR9","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.3233\/JAD-2010-091363","volume":"20","author":"L Agholme","year":"2010","unstructured":"Agholme L, Lindstr\u00f6m T, Kgedal K, Marcusson J, Hallbeck M (2010) An in vitro model for neuroscience: differentiation of SH-SY5Y cells into cells with morphological and biochemical characteristics of mature neurons. J Alzheimer\u2019s Dis 20:1069\u20131082","journal-title":"J Alzheimer\u2019s Dis"},{"key":"9506_CR10","unstructured":"De Bittencourt Pasquali MA, Ramos VM, Albanus RDO, Kunzler A, de Souza LHT, Dalmolin RJS, Gelain DP, Ribeiro L, Carro L, Moreira JCF (2014) Gene expression profile of NF-\u03baB, Nrf2, Glycolytic, and p53 pathways during the SH-SY5Y neuronal differentiation mediated by retinoic acid. Mol. Neurobiol.1-13"},{"key":"9506_CR11","doi-asserted-by":"crossref","unstructured":"Schneider L, Giordano S, Zelickson BR, S Johnson M, A Benavides G, Ouyang X, Fineberg N, Darley-Usmar VM, Zhang J (2011) Differentiation of SH-SY5Y cells to a neuronal phenotype changes cellular bioenergetics and the response to oxidative stress. Free Radic Biol Med Elsevier Inc.; 51: 2007\u20132017","DOI":"10.1016\/j.freeradbiomed.2011.08.030"},{"key":"9506_CR12","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.neuro.2008.11.001","volume":"30","author":"YT Cheung","year":"2009","unstructured":"Cheung YT, Lau WKW, Yu MS, Lai CSW, Yeung SC, So KF, Chang RCC (2009) Effects of all-trans-retinoic acid on human SH-SY5Y neuroblastoma as in vitro model in neurotoxicity research. Neurotoxicology 30:127\u2013135","journal-title":"Neurotoxicology"},{"key":"9506_CR13","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1146\/annurev.pharmtox.46.120604.141046","volume":"47","author":"TW Kensler","year":"2007","unstructured":"Kensler TW, Wakabayashi N, Biswal S (2007) Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu Rev Pharmacol Toxicol 47:89\u2013116","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"9506_CR14","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1093\/nar\/gkp1048","volume":"38","author":"W Li","year":"2010","unstructured":"Li W, Thakor N, Xu EY, Huang Y, Chen C, Yu R, Holcik M, Kong AN (2010) An internal ribosomal entry site mediates redox-sensitive translation of Nrf2. Nucleic Acids Res 38:778\u2013788","journal-title":"Nucleic Acids Res"},{"key":"9506_CR15","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.bcp.2012.11.016","volume":"85","author":"HK Bryan","year":"2013","unstructured":"Bryan HK, Olayanju A, Goldring CE, Park BK (2013) The Nrf2 cell defence pathway: Keap1-dependent and -independent mechanisms of regulation. Biochem Pharmacol Elsevier Inc 85:705\u2013717","journal-title":"Biochem Pharmacol Elsevier Inc"},{"key":"9506_CR16","first-page":"61","volume":"2","author":"J Johnson","year":"2009","unstructured":"Johnson J, Johnson D, Kraft AD, Calkins MJ (2009) The Nrf2-ARE pathway: an indicator and modulator of oxidative stress in neurodegeneration. Ann N Y Acad Sci 2:61\u201369","journal-title":"Ann N Y Acad Sci"},{"key":"9506_CR17","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.phrs.2008.09.003","volume":"58","author":"A Lau","year":"2008","unstructured":"Lau A, Villeneuve NF, Sun Z, Wong PK, Zhang DD (2008) Dual roles of Nrf2 in cancer. Pharmacol Res 58:262\u2013270","journal-title":"Pharmacol Res"},{"key":"9506_CR18","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1134\/S0006297913010033","volume":"78","author":"NK Zenkov","year":"2013","unstructured":"Zenkov NK, Menshchikova EB, Tkachev VO (2013) Keap1\/Nrf2\/ARE redox-sensitive signaling system as a pharmacological target. Biochem Biokhimii\u0361a 78:19\u201336","journal-title":"Biochem Biokhimii\u0361a"},{"key":"9506_CR19","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1016\/j.freeradbiomed.2009.06.029","volume":"47","author":"F Zhao","year":"2009","unstructured":"Zhao F, Wu T, Lau A, Jiang T, Huang Z, Wang XJ, Chen W, Wong PK, Zhang DD (2009) Nrf2 promotes neuronal cell differentiation. Free Radic Biol Med Elsevier Inc 47:867\u2013879","journal-title":"Free Radic Biol Med Elsevier Inc"},{"key":"9506_CR20","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/S0891-5849(99)00107-0","volume":"27","author":"H Wang","year":"1999","unstructured":"Wang H, Joseph J (1999) Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader. Free Radic Biol Med 27:612\u2013616","journal-title":"Free Radic Biol Med"},{"key":"9506_CR21","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1093\/jnci\/82.13.1107","volume":"82","author":"P Skehan","year":"1990","unstructured":"Skehan P, Storeng R, Scudiero D, Monks A, McMahon J, Vistica D, Warren JT, Bokesch H, Kenney S, Boyd MR (1990) New colorimetric cytotoxicity assay for anticancer-drug screening. J Natl Cancer Inst 82:1107\u20131112","journal-title":"J Natl Cancer Inst"},{"key":"9506_CR22","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1016\/j.tiv.2008.04.001","volume":"22","author":"A Zanotto-Filho","year":"2008","unstructured":"Zanotto-Filho A, Cammarota M, Gelain DP, Oliveira RB, Delgado-Ca\u00f1edo A, Dalmolin RJS, Pasquali MAB, Moreira JCF (2008) Retinoic acid induces apoptosis by a non-classical mechanism of ERK1\/2 activation. Toxicol Vitr 22:1205\u20131212","journal-title":"Toxicol Vitr"},{"key":"9506_CR23","first-page":"3333","volume":"31","author":"A Piskunov","year":"2012","unstructured":"Piskunov A, Rochette-Egly C (2012) A retinoic acid receptor RAR\u03b1 pool present in membrane lipid rafts forms complexes with G protein \u03b1Q to activate p38MAPK. Oncogene Nature Publ Group 31:3333\u20133345","journal-title":"Oncogene Nature Publ Group"},{"key":"9506_CR24","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.freeradbiomed.2013.02.008","volume":"66","author":"SK Niture","year":"2014","unstructured":"Niture SK, Khatri R, Jaiswal AK (2014) Regulation of Nrf2\u2014an update. Free Radic Biol Med Elsevier 66:36\u201344","journal-title":"Free Radic Biol Med Elsevier"},{"key":"9506_CR25","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1016\/j.bcp.2012.02.003","volume":"83","author":"G Filomeni","year":"2012","unstructured":"Filomeni G, Piccirillo S, Rotilio G, Ciriolo MR (2012) p38(MAPK) and ERK1\/2 dictate cell death\/survival response to different pro-oxidant stimuli via p53 and Nrf2 in neuroblastoma cells SH-SY5Y. Biochem Pharmacol Elsevier Inc 83:1349\u20131357","journal-title":"Biochem Pharmacol Elsevier Inc"},{"key":"9506_CR26","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1016\/j.freeradbiomed.2008.09.010","volume":"45","author":"KP Tan","year":"2008","unstructured":"Tan KP, Kosuge K, Yang M, Ito S (2008) NRF2 as a determinant of cellular resistance in retinoic acid cytotoxicity. Free Radic Biol Med Elsevier Inc 45:1663\u20131673","journal-title":"Free Radic Biol Med Elsevier Inc"},{"key":"9506_CR27","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.ccr.2012.05.016","volume":"22","author":"Y Mitsuishi","year":"2012","unstructured":"Mitsuishi Y, Taguchi K, Kawatani Y, Shibata T, Nukiwa T, Aburatani H, Yamamoto M, Motohashi H (2012) Nrf2 redirects glucose and glutamine into anabolic pathways in metabolic reprogramming. Cancer Cell Elsevier Inc 22:66\u201379","journal-title":"Cancer Cell Elsevier Inc"},{"key":"9506_CR28","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.cmet.2012.07.009","volume":"16","author":"JD Hayes","year":"2014","unstructured":"Hayes JD, Ashford MLJ (2014) Nrf2 orchestrates fuel partitioning for cell proliferation. Cell Metab 16:139\u2013141","journal-title":"Cell Metab"},{"key":"9506_CR29","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.tibs.2014.02.002","volume":"39","author":"JD Hayes","year":"2014","unstructured":"Hayes JD, Dinkova-Kostova AT (2014) The Nrf2 regulatory network provides an interface between redox and intermediary metabolism. Trends Biochem Sci 39:199\u2013218","journal-title":"Trends Biochem Sci"},{"key":"9506_CR30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.0022-202X.2004.23533.x","volume":"123","author":"S Nagpal","year":"2004","unstructured":"Nagpal S (2004) Retinoids: inducers of tumor\/growth suppressors. J Invest Dermatol 123:1\u20132","journal-title":"J Invest Dermatol"},{"key":"9506_CR31","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1146\/annurev.nutr.28.061807.155509","volume":"30","author":"N Noy","year":"2010","unstructured":"Noy N (2010) Between death and survival: retinoic acid in regulation of apoptosis. Annu Rev Nutr 30:201\u2013217","journal-title":"Annu Rev Nutr"},{"key":"9506_CR32","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1146\/annurev-pathol-011110-130303","volume":"6","author":"XH Tang","year":"2011","unstructured":"Tang XH, Gudas LJ (2011) Retinoids, retinoic acid receptors, and cancer. Annu Rev Pathol 6:345\u2013364","journal-title":"Annu Rev Pathol"},{"key":"9506_CR33","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.bbrc.2012.06.125","volume":"424","author":"J Qiao","year":"2012","unstructured":"Qiao J, Paul P, Lee S, Qiao L, Josifi E, Tiao JR, Chung DH (2012) PI3K\/AKT and ERK regulate retinoic acid-induced neuroblastoma cellular differentiation. Biochem Biophys Res Commun 424:421\u2013426","journal-title":"Biochem Biophys Res Commun"},{"key":"9506_CR34","doi-asserted-by":"crossref","first-page":"25297","DOI":"10.1074\/jbc.M201869200","volume":"277","author":"G L\u00f3pez-Carballo","year":"2002","unstructured":"L\u00f3pez-Carballo G, Moreno L, Masi\u00e1 S, P\u00e9rez P, Barettino D (2002) Activation of the phosphatidylinositol 3-kinase\/Akt signaling pathway by retinoic acid is required for neural differentiation of SH-SY5Y human neuroblastoma cells. J Biol Chem 277:25297\u201325304","journal-title":"J Biol Chem"},{"key":"9506_CR35","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/j.cellsig.2012.01.008","volume":"24","author":"PD Ray","year":"2012","unstructured":"Ray PD, Huang BW, Tsuji Y (2012) Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal 24:981\u2013990","journal-title":"Cell Signal"},{"key":"9506_CR36","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1210\/me.2007-0062","volume":"21","author":"S Masi\u00e1","year":"2007","unstructured":"Masi\u00e1 S, Alvarez S, de Lera AR, Barettino D (2007) Rapid, nongenomic actions of retinoic acid on phosphatidylinositol-3-kinase signaling pathway mediated by the retinoic acid receptor. Mol Endocrinol 21:2391\u20132402","journal-title":"Mol Endocrinol"},{"key":"9506_CR37","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.neuropharm.2013.11.004","volume":"79","author":"M Sandberg","year":"2014","unstructured":"Sandberg M, Patil J, D\u2019Angelo B, Weber SG, Mallard C (2014) NRF2-regulation in brain health and disease: implication of cerebral inflammation. Neuropharmacology 79:298\u2013306","journal-title":"Neuropharmacology"},{"key":"9506_CR38","unstructured":"Seeger C, Haussler R (1983) Effects of retinoic acid (RA) on the growth and phenotypic expression of several human neuroblastoma cell lines. 148: 21\u201330"}],"container-title":["Molecular Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s12035-015-9506-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-015-9506-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-015-9506-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-015-9506-6","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,6,1]],"date-time":"2019-06-01T22:42:30Z","timestamp":1559428950000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s12035-015-9506-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,11,5]]},"references-count":38,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2016,11]]}},"alternative-id":["9506"],"URL":"https:\/\/doi.org\/10.1007\/s12035-015-9506-6","relation":{},"ISSN":["0893-7648","1559-1182"],"issn-type":[{"value":"0893-7648","type":"print"},{"value":"1559-1182","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,11,5]]}}}