{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T02:58:56Z","timestamp":1792119536889,"version":"4.4.0"},"reference-count":56,"publisher":"Elsevier BV","issue":"5","license":[{"start":{"date-parts":[[2014,5,1]],"date-time":"2014-05-01T00:00:00Z","timestamp":1398902400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2014,5,1]],"date-time":"2014-05-01T00:00:00Z","timestamp":1398902400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["molpharm.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Pharmacology"],"published-print":{"date-parts":[[2014,5]]},"DOI":"10.1124\/mol.114.091728","type":"journal-article","created":{"date-parts":[[2014,2,26]],"date-time":"2014-02-26T05:04:04Z","timestamp":1393391044000},"page":"747-757","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":92,"title":["Morphine Induces Redox-Based Changes in Global DNA Methylation and Retrotransposon Transcription by Inhibition of Excitatory Amino Acid Transporter Type 3\u2013Mediated Cysteine Uptake"],"prefix":"10.1016","volume":"85","author":[{"given":"Malav","family":"Trivedi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayni","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaniel","family":"Hodgson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyang-Min","family":"Byun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Deth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1124\/mol.114.091728_bib1","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1093\/ije\/dys220","article-title":"Association between blood pressure and DNA methylation of retrotransposons and pro-inflammatory genes","volume":"42","author":"Alexeeff","year":"2013","journal-title":"Int J Epidemiol"},{"key":"10.1124\/mol.114.091728_bib2","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/nn1609","article-title":"Neuronal glutathione deficiency and age-dependent neurodegeneration in the EAAC1 deficient mouse","volume":"9","author":"Aoyama","year":"2006","journal-title":"Nat Neurosci"},{"key":"10.1124\/mol.114.091728_bib3","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1254\/jphs.08R01CR","article-title":"Regulation of neuronal glutathione synthesis","volume":"108","author":"Aoyama","year":"2008","journal-title":"J Pharmacol Sci"},{"key":"10.1124\/mol.114.091728_bib4","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/S0169-328X(98)00005-9","article-title":"mu-Opioid receptor down-regulation and cAMP-dependent protein kinase phosphorylation in a mouse model of chronic morphine tolerance","volume":"55","author":"Bernstein","year":"1998","journal-title":"Brain Res Mol Brain Res"},{"key":"10.1124\/mol.114.091728_bib5","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1007\/s00018-005-5277-y","article-title":"Regulation of the extracellular signal-regulated kinases following acute and chronic opioid treatment","volume":"62","author":"Bilecki","year":"2005","journal-title":"Cell Mol Life Sci"},{"key":"10.1124\/mol.114.091728_bib6","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1080\/13556210120056544","article-title":"Adaptative response of antioxidant enzymes in different areas of rat brain after repeated d-amphetamine administration","volume":"6","author":"Carvalho","year":"2001","journal-title":"Addict Biol"},{"key":"10.1124\/mol.114.091728_bib7","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1046\/j.1471-4159.2003.01630.x","article-title":"The glutamate transporters EAAT2 and EAAT3 mediate cysteine uptake in cortical neuron cultures","volume":"84","author":"Chen","year":"2003","journal-title":"J Neurochem"},{"key":"10.1124\/mol.114.091728_bib8","doi-asserted-by":"crossref","first-page":"33116","DOI":"10.1074\/jbc.C112.406975","article-title":"The mammalian de novo DNA methyltransferases Dnmt3a and Dnmt3b are also DNA 5-hydroxymethylcytosine dehydroxymethylases","volume":"287","author":"Chen","year":"2012","journal-title":"J Biol Chem"},{"key":"10.1124\/mol.114.091728_bib9","series-title":"S-adenosylmethionine-dependent methyltransferases: structures and functions","author":"Cheng","year":"1999"},{"key":"10.1124\/mol.114.091728_bib10","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1096\/fasebj.10.4.8647346","article-title":"S-Adenosylmethionine and methylation","volume":"10","author":"Chiang","year":"1996","journal-title":"FASEB J"},{"key":"10.1124\/mol.114.091728_bib11","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1038\/bjp.2008.100","article-title":"Cellular neuroadaptations to chronic opioids: tolerance, withdrawal and addiction","volume":"154","author":"Christie","year":"2008","journal-title":"Br J Pharmacol"},{"key":"10.1124\/mol.114.091728_bib12","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.ejphar.2011.06.014","article-title":"Fentanyl activates hypoxia-inducible factor 1 in neuronal SH-SY5Y cells and mice under non-hypoxic conditions in a \u03bc-opioid receptor-dependent manner","volume":"667","author":"Daijo","year":"2011","journal-title":"Eur J Pharmacol"},{"key":"10.1124\/mol.114.091728_bib13","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1101\/gad.2037511","article-title":"CpG islands and the regulation of transcription","volume":"25","author":"Deaton","year":"2011","journal-title":"Genes Dev"},{"key":"10.1124\/mol.114.091728_bib14","doi-asserted-by":"crossref","first-page":"e59068","DOI":"10.1371\/journal.pone.0059068","article-title":"Quality evaluation of methyl binding domain based kits for enrichment DNA-methylation sequencing","volume":"8","author":"De Meyer","year":"2013","journal-title":"PLoS ONE"},{"key":"10.1124\/mol.114.091728_bib15","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.alcohol.2008.12.003","article-title":"Effects of N-acetylcysteine on alcohol abstinence and alcohol-induced adverse effects in rats","volume":"43","author":"Ferreira Seiva","year":"2009","journal-title":"Alcohol"},{"key":"10.1124\/mol.114.091728_bib17","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.neuint.2004.10.006","article-title":"Differential regulation by protein kinases of activity and cell surface expression of glutamate transporters in neuron-enriched cultures","volume":"46","author":"Guillet","year":"2005","journal-title":"Neurochem Int"},{"key":"10.1124\/mol.114.091728_bib18","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.drugalcdep.2010.06.020","article-title":"The influence of heroin abuse on glutathione-dependent enzymes in human brain","volume":"113","author":"Gutowicz","year":"2011","journal-title":"Drug Alcohol Depend"},{"key":"10.1124\/mol.114.091728_bib19","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1007\/s00702-003-0049-z","article-title":"Role of neuronal glutamate transporter in the cysteine uptake and intracellular glutathione levels in cultured cortical neurons","volume":"110","author":"Himi","year":"2003","journal-title":"J Neural Transm"},{"key":"10.1124\/mol.114.091728_bib20","doi-asserted-by":"crossref","first-page":"197","DOI":"10.3233\/JAD-130101","article-title":"Soluble oligomers of amyloid-\u03b2 cause changes in redox state, DNA methylation, and gene transcription by inhibiting EAAT3 mediated cysteine uptake","volume":"36","author":"Hodgson","year":"2013","journal-title":"J Alzheimers Dis"},{"key":"10.1124\/mol.114.091728_bib21","doi-asserted-by":"crossref","first-page":"11187","DOI":"10.1523\/JNEUROSCI.0684-12.2012","article-title":"Opioid activation of toll-like receptor 4 contributes to drug reinforcement","volume":"32","author":"Hutchinson","year":"2012","journal-title":"J Neurosci"},{"key":"10.1124\/mol.114.091728_bib22","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1097\/00001756-200211150-00018","article-title":"Identification of addicsin\/GTRAP3-18 as a chronic morphine-augmented gene in amygdala","volume":"13","author":"Ikemoto","year":"2002","journal-title":"Neuroreport"},{"key":"10.1124\/mol.114.091728_bib23","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1097\/01.ALC.0000092061.92393.79","article-title":"Effects of ethanol on the rat glutamate excitatory amino acid transporter type 3 expressed in Xenopus oocytes: role of protein kinase C and phosphatidylinositol 3-kinase","volume":"27","author":"Kim","year":"2003","journal-title":"Alcohol Clin Exp Res"},{"key":"10.1124\/mol.114.091728_bib24","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/35057062","article-title":"Initial sequencing and analysis of the human genome","volume":"409","author":"Lander","year":"2001","journal-title":"Nature"},{"key":"10.1124\/mol.114.091728_bib25","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0006-8993(01)03047-5","article-title":"Cocaine activates redox-regulated transcription factors and induces TNF-alpha expression in human brain endothelial cells","volume":"920","author":"Lee","year":"2001","journal-title":"Brain Res"},{"key":"10.1124\/mol.114.091728_bib26","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nrn1604","article-title":"Epigenetic mechanisms in memory formation","volume":"6","author":"Levenson","year":"2005","journal-title":"Nat Rev Neurosci"},{"key":"10.1124\/mol.114.091728_bib27","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/j.lfs.2008.09.014","article-title":"Bradykinin stimulates glutamate uptake via both B1R and B2R activation in a human retinal pigment epithelial cells","volume":"83","author":"Lim","year":"2008","journal-title":"Life Sci"},{"key":"10.1124\/mol.114.091728_bib28","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.neulet.2004.11.016","article-title":"cAMP and protein kinase A contribute to the downregulation of spinal glutamate transporters after chronic morphine","volume":"376","author":"Lim","year":"2005","journal-title":"Neurosci Lett"},{"key":"10.1124\/mol.114.091728_bib29","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1038\/35065084","article-title":"Modulation of the neuronal glutamate transporter EAAC1 by the interacting protein GTRAP3-18","volume":"410","author":"Lin","year":"2001","journal-title":"Nature"},{"key":"10.1124\/mol.114.091728_bib30","first-page":"1720","article-title":"Expression of EAAT3 in prefrontal cortex and hippocampus in CPP reinstatement rats induced by morphine","volume":"27","author":"Liu","year":"2011","journal-title":"Chinese Journal of Pathophysiology"},{"key":"10.1124\/mol.114.091728_bib31","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","article-title":"Protein measurement with the Folin phenol reagent","volume":"193","author":"Lowry","year":"1951","journal-title":"J Biol Chem"},{"key":"10.1124\/mol.114.091728_bib32","doi-asserted-by":"crossref","first-page":"8312","DOI":"10.1523\/JNEUROSCI.22-18-08312.2002","article-title":"Chronic morphine induces downregulation of spinal glutamate transporters: implications in morphine tolerance and abnormal pain sensitivity","volume":"22","author":"Mao","year":"2002","journal-title":"J Neurosci"},{"key":"10.1124\/mol.114.091728_bib33","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.pnpbp.2006.10.001","article-title":"An open-label trial of N-acetylcysteine for the treatment of cocaine dependence: a pilot study","volume":"31","author":"Mardikian","year":"2007","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"10.1124\/mol.114.091728_bib34","doi-asserted-by":"crossref","first-page":"3035","DOI":"10.1073\/pnas.1015483108","article-title":"Cocaine dynamically regulates heterochromatin and repetitive element unsilencing in nucleus accumbens","volume":"108","author":"Maze","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1124\/mol.114.091728_bib35","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/j.1749-6632.2010.05893.x","article-title":"The epigenetic landscape of addiction","volume":"1216","author":"Maze","year":"2011","journal-title":"Ann N Y Acad Sci"},{"key":"10.1124\/mol.114.091728_bib36","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.nlm.2007.07.016","article-title":"DNA methylation and histone acetylation work in concert to regulate memory formation and synaptic plasticity","volume":"89","author":"Miller","year":"2008","journal-title":"Neurobiol Learn Mem"},{"key":"10.1124\/mol.114.091728_bib37","doi-asserted-by":"crossref","first-page":"763","DOI":"10.2174\/0929867013372904","article-title":"Thiols in cellular redox signalling and control","volume":"8","author":"Moran","year":"2001","journal-title":"Curr Med Chem"},{"key":"10.1124\/mol.114.091728_bib38","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1124\/jpet.104.066548","article-title":"In vivo regulation of extracellular signal-regulated protein kinase (ERK) and protein kinase B (Akt) phosphorylation by acute and chronic morphine","volume":"310","author":"Muller","year":"2004","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/mol.114.091728_bib39","doi-asserted-by":"crossref","first-page":"e56927","DOI":"10.1371\/journal.pone.0056927","article-title":"Age-dependent decrease and alternative splicing of methionine synthase mRNA in human cerebral cortex and an accelerated decrease in autism","volume":"8","author":"Muratore","year":"2013","journal-title":"PLoS ONE"},{"key":"10.1124\/mol.114.091728_bib40","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1111\/j.1471-4159.2006.03978.x","article-title":"The neuronal excitatory amino acid transporter EAAC1\/EAAT3: does it represent a major actor at the brain excitatory synapse?","volume":"98","author":"Nieoullon","year":"2006","journal-title":"J Neurochem"},{"key":"10.1124\/mol.114.091728_bib41","doi-asserted-by":"crossref","first-page":"e23332","DOI":"10.1371\/journal.pone.0023332","article-title":"The global DNA methylation surrogate LINE-1 methylation is correlated with MGMT promoter methylation and is a better prognostic factor for glioma","volume":"6","author":"Ohka","year":"2011","journal-title":"PLoS ONE"},{"key":"10.1124\/mol.114.091728_bib42","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/0163-7258(95)02004-7","article-title":"Redox signalling and the control of cell growth and death","volume":"68","author":"Powis","year":"1995","journal-title":"Pharmacol Ther"},{"key":"10.1124\/mol.114.091728_bib44","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/35038572","article-title":"Mobile elements and the human genome","volume":"1","author":"Prak","year":"2000","journal-title":"Nat Rev Genet"},{"key":"10.1124\/mol.114.091728_bib45","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1124\/jpet.111.179317","article-title":"Chronic N-acetylcysteine during abstinence or extinction after cocaine self-administration produces enduring reductions in drug seeking","volume":"337","author":"Reichel","year":"2011","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/mol.114.091728_bib47","doi-asserted-by":"crossref","first-page":"e134","DOI":"10.1038\/tp.2012.61","article-title":"Evidence of oxidative damage and inflammation associated with low glutathione redox status in the autism brain","volume":"2","author":"Rose","year":"2012","journal-title":"Transcult Psychiatry"},{"key":"10.1124\/mol.114.091728_bib48","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.tins.2010.04.001","article-title":"LINE-1 retrotransposons: mediators of somatic variation in neuronal genomes?","volume":"33","author":"Singer","year":"2010","journal-title":"Trends Neurosci"},{"key":"10.1124\/mol.114.091728_bib49","doi-asserted-by":"crossref","first-page":"17454","DOI":"10.1523\/JNEUROSCI.1357-12.2012","article-title":"Morphine epigenomically regulates behavior through alterations in histone H3 lysine 9 dimethylation in the nucleus accumbens","volume":"32","author":"Sun","year":"2012","journal-title":"J Neurosci"},{"key":"10.1124\/mol.114.091728_bib50","doi-asserted-by":"crossref","first-page":"92","DOI":"10.3389\/fnins.2012.00092","article-title":"Role of a redox-based methylation switch in mRNA life cycle (pre- and post-transcriptional maturation) and protein turnover: implications in neurological disorders","volume":"6","author":"Trivedi","year":"2012","journal-title":"Front Neurosci"},{"issue":"Spec No 1","key":"10.1124\/mol.114.091728_bib51","doi-asserted-by":"crossref","first-page":"R139","DOI":"10.1093\/hmg\/ddi100","article-title":"The impact of metabolism on DNA methylation","volume":"14","author":"Ulrey","year":"2005","journal-title":"Hum Mol Genet"},{"key":"10.1124\/mol.114.091728_bib52","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1111\/j.1530-0277.2010.01343.x","article-title":"Ethanol lowers glutathione in rat liver and brain and inhibits methionine synthase in a cobalamin-dependent manner","volume":"35","author":"Waly","year":"2011","journal-title":"Alcohol Clin Exp Res"},{"key":"10.1124\/mol.114.091728_bib53","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/sj.mp.4001476","article-title":"Activation of methionine synthase by insulin-like growth factor-1 and dopamine: a target for neurodevelopmental toxins and thimerosal","volume":"9","author":"Waly","year":"2004","journal-title":"Mol Psychiatry"},{"key":"10.1124\/mol.114.091728_bib54","doi-asserted-by":"crossref","first-page":"18357","DOI":"10.1074\/jbc.M109.015453","article-title":"Differential modulation of \u03bc- and \u03b4-opioid receptor agonists by endogenous RGS4 protein in SH-SY5Y cells","volume":"284","author":"Wang","year":"2009","journal-title":"J Biol Chem"},{"key":"10.1124\/mol.114.091728_bib55","doi-asserted-by":"crossref","first-page":"9404","DOI":"10.1523\/JNEUROSCI.3351-08.2008","article-title":"A dominant role of GTRAP3-18 in neuronal glutathione synthesis","volume":"28","author":"Watabe","year":"2008","journal-title":"J Neurosci"},{"key":"10.1124\/mol.114.091728_bib56","doi-asserted-by":"crossref","first-page":"4775","DOI":"10.1523\/JNEUROSCI.23-11-04775.2003","article-title":"Morphine withdrawal increases glutamate uptake and surface expression of glutamate transporter GLT1 at hippocampal synapses","volume":"23","author":"Xu","year":"2003","journal-title":"J Neurosci"},{"key":"10.1124\/mol.114.091728_bib57","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1111\/j.1742-7843.2006.pto_461.x","article-title":"Heroin-administered mice involved in oxidative stress and exogenous antioxidant-alleviated withdrawal syndrome","volume":"99","author":"Xu","year":"2006","journal-title":"Basic Clin Pharmacol Toxicol"},{"key":"10.1124\/mol.114.091728_bib58","doi-asserted-by":"crossref","first-page":"21703","DOI":"10.1074\/jbc.M800809200","article-title":"Morphine induces ubiquitin-proteasome activity and glutamate transporter degradation","volume":"283","author":"Yang","year":"2008","journal-title":"J Biol Chem"},{"key":"10.1124\/mol.114.091728_bib60","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.toxlet.2013.12.002","article-title":"Nicotine decreases the activity of glutamate transporter type 3","volume":"225","author":"Yoon","year":"2014","journal-title":"Toxicol Lett"}],"container-title":["Molecular Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0026895X24039178?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0026895X24039178?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1124\/mol.114.091728","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T11:20:39Z","timestamp":1739964039000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0026895X24039178"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,5]]},"references-count":56,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2014,5]]}},"alternative-id":["S0026895X24039178"],"URL":"https:\/\/doi.org\/10.1124\/mol.114.091728","relation":{},"ISSN":["0026-895X"],"issn-type":[{"value":"0026-895X","type":"print"}],"subject":[],"published":{"date-parts":[[2014,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Morphine Induces Redox-Based Changes in Global DNA Methylation and Retrotransposon Transcription by Inhibition of Excitatory Amino Acid Transporter Type 3\u2013Mediated Cysteine Uptake","name":"articletitle","label":"Article Title"},{"value":"Molecular Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1124\/mol.114.091728","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2014 by The American Society for Pharmacology and Experimental Therapeutics","name":"copyright","label":"Copyright"}]}}