{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:17:06Z","timestamp":1760059026204,"version":"build-2065373602"},"reference-count":80,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:00:00Z","timestamp":1747180800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institute of Health\u2019s National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL144146","R01HL168500"],"award-info":[{"award-number":["R01HL144146","R01HL168500"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Diabetes mellitus, especially type 2 diabetes mellitus (T2DM), is a major health problem worldwide and has become a leading cause of mortality. As a common complication of patients with T2DM, cardiac autonomic dysfunction (including sympathetic overactivation and reduced vagal tone) is associated with a higher risk of arrhythmia-related sudden cardiac death. Our previous study found that T2DM-elevated hydrogen peroxide (H2O2) levels in atrioventricular ganglion (AVG) neurons contribute to the decrease in cardiac vagal function and ventricular arrhythmogenesis through inhibition of N-type Ca2+ channels (Cav2.2). In the present study, treatment with exogenous H2O2 in differentiated NG108-15 cells increased REST expression and decreased Cav2.2-\u03b1 expression. Adenoviral catalase gene transfection into the AVG neurons significantly reduced the REST levels elevated by a high-fat diet plus streptozotocin-induced T2DM. Lentiviral REST shRNA transfection markedly increased Cav2.2-\u03b1 expression in the AVG neurons from T2DM rats. REST shRNA also activated N-type Ca2+ channels and increased cell excitability of AVG neurons in T2DM rats. Additionally, REST shRNA markedly improved cardiac vagal activation in T2DM rats. The present study suggests that the H2O2-REST-Cav2.2 channel signaling axis could be a potential therapeutic target to normalize cardiac vagal dysfunction and its related cardiac complications in T2DM.<\/jats:p>","DOI":"10.3390\/antiox14050588","type":"journal-article","created":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T10:27:41Z","timestamp":1747218461000},"page":"588","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hydrogen Peroxide-Induced Re-Expression of Repressor Element 1-Silencing Transcription Factor Contributes to Cardiac Vagal Dysfunction in Type 2 Diabetes Mellitus"],"prefix":"10.3390","volume":"14","author":[{"given":"Dongze","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1662-2088","authenticated-orcid":false,"given":"Huiyin","family":"Tu","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenfeng","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5688-6707","authenticated-orcid":false,"given":"Michael C.","family":"Wadman","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5407-2761","authenticated-orcid":false,"given":"Yu-Long","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA"},{"name":"Department of Cellular & Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.2337\/diacare.21.7.1138","article-title":"Mortality in adults with and without diabetes in a national cohort of the U.S. population, 1971\u20131993","volume":"21","author":"Gu","year":"1998","journal-title":"Diabetes Care"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"319","DOI":"10.4093\/dmj.2018.0060","article-title":"Diabetes Mellitus and Cause-Specific Mortality: A Population-Based Study","volume":"43","author":"Li","year":"2019","journal-title":"Diabetes Metab. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1186\/s12933-020-01159-5","article-title":"Global trend of diabetes mortality attributed to vascular complications, 2000\u20132016","volume":"19","author":"Ling","year":"2020","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1093\/ije\/dyaa270","article-title":"Declining mortality in older people with type 2 diabetes masks rising excess risks at younger ages: A population-based study of all-cause and cause-specific mortality over 13 years","volume":"50","author":"Sacre","year":"2021","journal-title":"Int. J. Epidemiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2611","DOI":"10.1007\/s00125-024-06242-0","article-title":"Cardiovascular autonomic neuropathy in diabetes: An update with a focus on management","volume":"67","author":"Eleftheriadou","year":"2024","journal-title":"Diabetologia"},{"doi-asserted-by":"crossref","unstructured":"Benichou, T., Pereira, B., Mermillod, M., Tauveron, I., Pfabigan, D., Maqdasy, S., and Dutheil, F. (2018). Heart rate variability in type 2 diabetes mellitus: A systematic review and meta-analysis. PLoS ONE, 13.","key":"ref_6","DOI":"10.1371\/journal.pone.0195166"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1046\/j.1464-5491.2001.00442.x","article-title":"Abnormal cardiovascular reflex tests are predictors of mortality in Type 2 diabetes mellitus","volume":"18","author":"Chen","year":"2001","journal-title":"Diabet. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e002480","DOI":"10.1136\/bmjdrc-2021-002480","article-title":"Cardiac autonomic neuropathy and risk of cardiovascular disease and mortality in type 1 and type 2 diabetes: A meta-analysis","volume":"9","author":"Chowdhury","year":"2021","journal-title":"BMJ Open Diabetes Res. Care"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1161\/ATVBAHA.120.314102","article-title":"Type 2 Diabetes Mellitus Is Independently Associated With Decreased Neural Baroreflex Sensitivity: The Paris Prospective Study III","volume":"40","author":"Cseh","year":"2020","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1111\/j.1464-5491.2010.03221.x","article-title":"Cardiovascular autonomic neuropathy contributes to left ventricular diastolic dysfunction in subjects with Type 2 diabetes and impaired glucose tolerance undergoing coronary angiography","volume":"28","author":"Dinh","year":"2011","journal-title":"Diabet. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.2337\/diacare.26.6.1895","article-title":"The association between cardiovascular autonomic neuropathy and mortality in individuals with diabetes: A meta-analysis","volume":"26","author":"Maser","year":"2003","journal-title":"Diabetes Care"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1536\/ihj.18-455","article-title":"Clinical Implications of Baroreflex Sensitivity in Type 2 Diabetes","volume":"60","author":"Sakamoto","year":"2019","journal-title":"Int. Heart J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1002\/dmrr.1239","article-title":"Cardiovascular autonomic neuropathy in diabetes: Clinical impact, assessment, diagnosis, and management","volume":"27","author":"Spallone","year":"2011","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"715","DOI":"10.4103\/ijem.IJEM_448_16","article-title":"Arrhythmias in Type 2 Diabetes Mellitus","volume":"21","author":"Agarwal","year":"2017","journal-title":"Indian. J. Endocrinol. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1016\/j.hrthm.2024.05.063","article-title":"Sudden cardiac death due to ventricular arrhythmia in diabetes mellitus: A bench to bedside review","volume":"21","author":"Chakraborty","year":"2024","journal-title":"Heart Rhythm."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1161\/01.CIR.0000136993.34344.41","article-title":"Temporal trends in coronary heart disease mortality and sudden cardiac death from 1950 to 1999: The Framingham Heart Study","volume":"110","author":"Fox","year":"2004","journal-title":"Circulation"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"109119","DOI":"10.1016\/j.diabres.2021.109119","article-title":"IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045","volume":"183","author":"Sun","year":"2022","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s10741-010-9216-0","article-title":"Vagus nerve stimulation: From pre-clinical to clinical application: Challenges and future directions","volume":"16","author":"Schwartz","year":"2011","journal-title":"Heart Fail. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1016\/j.jacep.2018.05.003","article-title":"Effects of Vagal Nerve Stimulation on Ganglionated Plexi Nerve Activity and Ventricular Rate in Ambulatory Dogs With Persistent Atrial Fibrillation","volume":"4","author":"Jiang","year":"2018","journal-title":"JACC Clin. Electrophysiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.cardiores.2006.12.001","article-title":"Autonomic modulation of electrical restitution, alternans and ventricular fibrillation initiation in the isolated heart","volume":"73","author":"Ng","year":"2007","journal-title":"Cardiovasc. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.jacbts.2019.02.009","article-title":"Neuromodulation for the Treatment of Heart Rhythm Disorders","volume":"4","author":"Waldron","year":"2019","journal-title":"JACC Basic. Transl. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1080\/17434440.2019.1643234","article-title":"The role of low-level vagus nerve stimulation in cardiac therapy","volume":"16","author":"Wang","year":"2019","journal-title":"Expert. Rev. Med. Devices"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1016\/j.hrthm.2018.03.012","article-title":"Antiarrhythmic effects of vagal nerve stimulation after cardiac sympathetic denervation in the setting of chronic myocardial infarction","volume":"15","author":"Yamaguchi","year":"2018","journal-title":"Heart Rhythm."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2936","DOI":"10.2337\/diacare.27.12.2936","article-title":"Sympathetic and parasympathetic neuropathy are frequent in both type 1 and type 2 diabetic patients","volume":"27","author":"Freccero","year":"2004","journal-title":"Diabetes Care"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"C1119","DOI":"10.1152\/ajpcell.00315.2011","article-title":"Alterations of calcium channels and cell excitability in intracardiac ganglion neurons from type 2 diabetic rats","volume":"302","author":"Liu","year":"2012","journal-title":"Am. J. Physiol. Cell Physiol."},{"doi-asserted-by":"crossref","unstructured":"Zhang, D., Tu, H., Hu, W., Duan, B., Zimmerman, M.C., and Li, Y.L. (2022). Hydrogen peroxide scavenging restores N-type calcium channels in cardiac vagal postganglionic neurons and mitigates myocardial infarction-evoked ventricular arrhythmias in type 2 diabetes. Front. Cardiovasc. Med., 9.","key":"ref_26","DOI":"10.3389\/fcvm.2022.871852"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"14872","DOI":"10.1523\/JNEUROSCI.4286-14.2015","article-title":"REST Regulates Non\u2013Cell-Autonomous Neuronal Differentiation and Maturation of Neural Progenitor Cells via Secretogranin II","volume":"35","author":"Kim","year":"2015","journal-title":"J. Neurosci."},{"doi-asserted-by":"crossref","unstructured":"Su, X.J., Shen, B.D., Wang, K., Song, Q.X., Yang, X., Wu, D.S., Shen, H.X., and Zhu, C. (2022). Roles of the Neuron-Restrictive Silencer Factor in the Pathophysiological Process of the Central Nervous System. Front. Cell Dev. Biol., 10.","key":"ref_28","DOI":"10.3389\/fcell.2022.834620"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.molcel.2004.05.026","article-title":"Localized domains of G9a-mediated histone methylation are required for silencing of neuronal genes","volume":"14","author":"Roopra","year":"2004","journal-title":"Mol. Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1038\/nmeth.1246","article-title":"Genome-wide analysis of transcription factor binding sites based on ChIP-Seq data","volume":"5","author":"Valouev","year":"2008","journal-title":"Nat. Methods"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s12031-014-0474-5","article-title":"NRSF: An angel or a devil in neurogenesis and neurological diseases","volume":"56","author":"Song","year":"2015","journal-title":"J. Mol. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.molcel.2005.08.030","article-title":"Downregulated REST transcription factor is a switch enabling critical potassium channel expression and cell proliferation","volume":"20","author":"Cheong","year":"2005","journal-title":"Mol. Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/0959-4388(95)80060-3","article-title":"Silencing is golden: Negative regulation in the control of neuronal gene transcription","volume":"5","author":"Schoenherr","year":"1995","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/0092-8674(95)90298-8","article-title":"REST: A mammalian silencer protein that restricts sodium channel gene expression to neurons","volume":"80","author":"Chong","year":"1995","journal-title":"Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1634\/stemcells.2006-0207","article-title":"RE1 Silencing transcription factor maintains a repressive chromatin environment in embryonic hippocampal neural stem cells","volume":"25","author":"Greenway","year":"2007","journal-title":"Stem Cells"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1261\/rna.1127009","article-title":"Regulation of neural macroRNAs by the transcriptional repressor REST","volume":"15","author":"Johnson","year":"2009","journal-title":"RNA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s00441-014-1963-0","article-title":"RE-1 silencing transcription factor (REST): A regulator of neuronal development and neuronal\/endocrine function","volume":"359","author":"Thiel","year":"2015","journal-title":"Cell Tissue Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"ENEURO.0010-15.2015","DOI":"10.1523\/ENEURO.0010-15.2015","article-title":"The transcription repressor REST in adult neurons: Physiology, pathology, and diseases","volume":"2","author":"Baldelli","year":"2015","journal-title":"eNeuro"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1111\/jnc.15755","article-title":"Neuron-restrictive silencer factor\/repressor element 1-silencing transcription factor (NRSF\/REST) controls spatial K(+) buffering in primary cortical astrocytes","volume":"165","author":"Centonze","year":"2023","journal-title":"J. Neurochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.conb.2017.12.008","article-title":"REST, a master transcriptional regulator in neurodegenerative disease","volume":"48","author":"Hwang","year":"2018","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/s41586-019-1647-8","article-title":"Regulation of lifespan by neural excitation and REST","volume":"574","author":"Zullo","year":"2019","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2994","DOI":"10.1038\/emboj.2013.231","article-title":"REST\/NRSF-mediated intrinsic homeostasis protects neuronal networks from hyperexcitability","volume":"32","author":"Pozzi","year":"2013","journal-title":"Embo J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"8347","DOI":"10.1523\/JNEUROSCI.22-19-08347.2002","article-title":"Repressor element-1 silencing transcription\/neuron-restrictive silencer factor is required for neural sodium channel expression during development of Xenopus","volume":"22","author":"Fuentes","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"15489","DOI":"10.1074\/jbc.M111.310763","article-title":"Transcriptional regulation of T-type calcium channel CaV3.2: Bi-directionality by early growth response 1 (Egr1) and repressor element 1 (RE-1) protein-silencing transcription factor (REST)","volume":"287","author":"Schaub","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"6729","DOI":"10.1523\/JNEUROSCI.0091-07.2007","article-title":"A new binding motif for the transcriptional repressor REST uncovers large gene networks devoted to neuronal functions","volume":"27","author":"Otto","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3862","DOI":"10.1093\/nar\/gkl525","article-title":"Identification of the REST regulon reveals extensive transposable element-mediated binding site duplication","volume":"34","author":"Johnson","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5098","DOI":"10.1074\/jbc.272.8.5098","article-title":"Isolation and characterization of the 5\u2032-upstream region of the human N-type calcium channel alpha1B subunit gene. Chromosomal localization and promoter analysis","volume":"272","author":"Kim","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"181","DOI":"10.4196\/kjpp.2013.17.3.181","article-title":"Contradictory Effects of Superoxide and Hydrogen Peroxide on KCa3.1 in Human Endothelial Cells","volume":"17","author":"Choi","year":"2013","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"ref_49","first-page":"012","article-title":"Nicotinic acetylcholine receptors and cardiac vagal activity in rats with type 2 diabetes","volume":"6","author":"Liu","year":"2015","journal-title":"J. Diabetes Metab."},{"doi-asserted-by":"crossref","unstructured":"Zhang, D., Tu, H., Wang, C., Cao, L., Muelleman, R.L., Wadman, M.C., and Li, Y.L. (2017). Correlation of ventricular arrhythmogenesis with neuronal remodeling of cardiac postganglionic parasympathetic neurons in the late stage of heart failure after myocardial infarction. Front. Neurosci., 11.","key":"ref_50","DOI":"10.3389\/fnins.2017.00252"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e007457","DOI":"10.1161\/JAHA.117.007457","article-title":"Reduced N-Type Ca(2+) Channels in Atrioventricular Ganglion Neurons Are Involved in Ventricular Arrhythmogenesis","volume":"7","author":"Zhang","year":"2018","journal-title":"J. Am. Heart Assoc."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"C132","DOI":"10.1152\/ajpcell.00223.2013","article-title":"Heart failure-induced changes of voltage-gated Ca2+ channels and cell excitability in rat cardiac postganglionic neurons","volume":"306","author":"Tu","year":"2014","journal-title":"Am. J. Physiol. Cell Physiol."},{"doi-asserted-by":"crossref","unstructured":"Hu, W., Zhang, D., Tu, H., and Li, Y.L. (2021). Reduced Cell Excitability of Cardiac Postganglionic Parasympathetic Neurons Correlates With Myocardial Infarction-Induced Fatal Ventricular Arrhythmias in Type 2 Diabetes Mellitus. Front. Neurosci., 15.","key":"ref_53","DOI":"10.3389\/fnins.2021.721364"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/978-1-61779-043-0_18","article-title":"Reverse phase protein microarrays: Fluorometric and colorimetric detection","volume":"723","author":"Gallagher","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.bbrc.2012.05.076","article-title":"Changes of calcium channel mRNA, protein and current in NG108-15 cells after cell differentiation","volume":"423","author":"Liu","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/1756-6606-2-36","article-title":"Action potential evoked transmitter release in central synapses: Insights from the developing calyx of Held","volume":"2","author":"Wang","year":"2009","journal-title":"Mol. Brain"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5630","DOI":"10.1091\/mbc.e05-07-0687","article-title":"Distinct profiles of REST interactions with its target genes at different stages of neuronal development","volume":"16","author":"Sun","year":"2005","journal-title":"Mol. Biol. Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"357","DOI":"10.4137\/BBI.S13279","article-title":"ChIP-Seq Data Mining: Remarkable Differences in NRSF\/REST Target Genes between Human ESC and ESC-Derived Neurons","volume":"7","author":"Satoh","year":"2013","journal-title":"Bioinform. Biol. Insights"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"317","DOI":"10.2217\/fnl.09.1","article-title":"REST and the RESTless: In stem cells and beyond","volume":"4","author":"Gopalakrishnan","year":"2009","journal-title":"Future Neurol."},{"doi-asserted-by":"crossref","unstructured":"Wu, J., and Xie, X. (2006). Comparative sequence analysis reveals an intricate network among REST, CREB and miRNA in mediating neuronal gene expression. Genome Biol., 7.","key":"ref_60","DOI":"10.1186\/gb-2006-7-9-r85"},{"doi-asserted-by":"crossref","unstructured":"Johnson, R., Teh, C.H., Kunarso, G., Wong, K.Y., Srinivasan, G., Cooper, M.L., Volta, M., Chan, S.S., Lipovich, L., and Pollard, S.M. (2008). REST regulates distinct transcriptional networks in embryonic and neural stem cells. PLoS Biol., 6.","key":"ref_61","DOI":"10.1371\/journal.pbio.0060256"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e01267","DOI":"10.7554\/eLife.01267","article-title":"The transcription factor NRSF contributes to epileptogenesis by selective repression of a subset of target genes","volume":"3","author":"McClelland","year":"2014","journal-title":"Elife"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1523\/JNEUROSCI.18-04-01280.1998","article-title":"Neuronal expression of zinc finger transcription factor REST\/NRSF\/XBR gene","volume":"18","author":"Palm","year":"1998","journal-title":"J. Neurosci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.nbd.2006.04.020","article-title":"Regulation and role of REST and REST4 variants in modulation of gene expression in in vivo and in vitro in epilepsy models","volume":"24","author":"Spencer","year":"2006","journal-title":"Neurobiol. Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1523\/JNEUROSCI.23-06-02112.2003","article-title":"Ischemic insults derepress the gene silencer REST in neurons destined to die","volume":"23","author":"Calderone","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4170","DOI":"10.1073\/pnas.0611704104","article-title":"Ischemic insults promote epigenetic reprogramming of mu opioid receptor expression in hippocampal neurons","volume":"104","author":"Formisano","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"E962","DOI":"10.1073\/pnas.1121568109","article-title":"Repressor element-1 silencing transcription factor (REST)-dependent epigenetic remodeling is critical to ischemia-induced neuronal death","volume":"109","author":"Noh","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"doi-asserted-by":"crossref","unstructured":"Jin, L., Liu, Y., Wu, Y., Huang, Y., and Zhang, D. (2023). REST Is Not Resting: REST\/NRSF in Health and Disease. Biomolecules, 13.","key":"ref_68","DOI":"10.3390\/biom13101477"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e76754","DOI":"10.7554\/eLife.76754","article-title":"Repressor element 1-silencing transcription factor deficiency yields profound hearing loss through Kv7.4 channel upsurge in auditory neurons and hair cells","volume":"11","author":"Zhang","year":"2022","journal-title":"eLife"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"13235","DOI":"10.1523\/JNEUROSCI.1981-10.2010","article-title":"Transcriptional control of KCNQ channel genes and the regulation of neuronal excitability","volume":"30","author":"Mucha","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"9881","DOI":"10.1073\/pnas.93.18.9881","article-title":"Identification of potential target genes for the neuron-restrictive silencer factor","volume":"93","author":"Schoenherr","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neuroscience.2009.12.021","article-title":"Neuron-restrictive silencer factor causes epigenetic silencing of Kv4.3 gene after peripheral nerve injury","volume":"166","author":"Uchida","year":"2010","journal-title":"Neuroscience"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"4806","DOI":"10.1523\/JNEUROSCI.5541-09.2010","article-title":"Epigenetic gene silencing underlies C-fiber dysfunctions in neuropathic pain","volume":"30","author":"Uchida","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1113\/jphysiol.1992.sp019344","article-title":"Voltage-dependent sodium and calcium currents in cultured parasympathetic neurones from rat intracardiac ganglia","volume":"456","author":"Xu","year":"1992","journal-title":"J. Physiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"5953685","DOI":"10.1155\/2019\/5953685","article-title":"Circulating Oxidative Stress Biomarkers in Clinical Studies on Type 2 Diabetes and Its Complications","volume":"2019","author":"Bigagli","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1089\/ars.2012.4886","article-title":"Methods for detection of mitochondrial and cellular reactive oxygen species","volume":"20","author":"Dikalov","year":"2014","journal-title":"Antioxid. Redox. Signal"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.yjmcc.2014.01.018","article-title":"An overview of mechanisms of redox signaling","volume":"73","author":"Forman","year":"2014","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1007\/s00109-013-1067-4","article-title":"Imaging ROS signaling in cells and animals","volume":"91","author":"Wang","year":"2013","journal-title":"J. Mol. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1002\/stem.1430","article-title":"High throughput screening for inhibitors of REST in neural derivatives of human embryonic stem cells reveals a chemical compound that promotes expression of neuronal genes","volume":"31","author":"Charbord","year":"2013","journal-title":"Stem Cells"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"8018","DOI":"10.1128\/MCB.24.18.8018-8025.2004","article-title":"Activation of REST\/NRSF target genes in neural stem cells is sufficient to cause neuronal differentiation","volume":"24","author":"Su","year":"2004","journal-title":"Mol. Cell. Biol."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/14\/5\/588\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:32:21Z","timestamp":1760031141000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/14\/5\/588"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,14]]},"references-count":80,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["antiox14050588"],"URL":"https:\/\/doi.org\/10.3390\/antiox14050588","relation":{},"ISSN":["2076-3921"],"issn-type":[{"type":"electronic","value":"2076-3921"}],"subject":[],"published":{"date-parts":[[2025,5,14]]}}}