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dc.creatorLi, Jian-Guo
dc.creatorBarrero, Carlos
dc.creatorGupta, Sapna
dc.creatorKruger, Warren D.
dc.creatorMerali, Salim
dc.creatorPractico, Domenico
dc.date.accessioned2023-03-07T20:01:16Z
dc.date.available2023-03-07T20:01:16Z
dc.date.issued2016-11-29
dc.identifier.citationLi, J.-G., Barrero, C., Gupta, S., Kruger, W.D., Merali, S. and Praticò, D. (2017), Homocysteine modulates 5-lipoxygenase expression level via DNA methylation. Aging Cell, 16: 273-280. https://doi.org/10.1111/acel.12550
dc.identifier.issn1474-9726
dc.identifier.doihttp://dx.doi.org/10.34944/dspace/8357
dc.identifier.urihttp://hdl.handle.net/20.500.12613/8390
dc.description.abstractElevated levels of homocysteinemia (Hcy), a risk factor for late-onset Alzheimer's disease (AD), have been associated with changes in cell methylation. Alzheimer's disease is characterized by an upregulation of the 5-lipoxygenase (5LO), whose promoter is regulated by methylation. However, whether Hcy activates 5LO enzymatic pathway by influencing the methylation status of its promoter remains unknown. Brains from mice with high Hcy were assessed for the 5LO pathway and neuronal cells exposed to Hcy implemented to study the mechanism(s) regulating 5LO expression levels and the effect on amyloid β formation. Diet- and genetically induced high Hcy resulted in 5LO protein and mRNA upregulation, which was associated with a significant increase of the S-adenosylhomocysteine (SAH)/S-adenosylmethionine ratio, and reduced DNA methyltrasferases and hypomethylation of 5-lipoxygenase DNA. In vitro studies confirmed these results and demonstrated that the mechanism involved in the Hcy-dependent 5LO activation and amyloid β formation is DNA hypomethylation secondary to the elevated levels of SAH. Taken together these findings represent the first demonstration that Hcy directly influences 5LO expression levels and establish a previously unknown cross talk between these two pathways, which is highly relevant for AD pathogenesis. The discovery of such a novel link not only provides new mechanistic insights in the neurobiology of Hcy, but most importantly new therapeutic opportunities for the individuals bearing this risk factor for the disease.
dc.format.extent8 pages
dc.languageEnglish
dc.language.isoeng
dc.relation.ispartofFaculty/ Researcher Works
dc.relation.haspartAging Cell, Vol. 16, Iss. 2
dc.relation.isreferencedbyWiley
dc.rightsAttribution CC BY
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/
dc.titleHomocysteine modulates 5-lipoxygenase expression level via DNA methylation
dc.typeText
dc.type.genreJournal article
dc.contributor.groupCenter for Translational Medicine (Temple University)
dc.description.departmentPharmacology
dc.description.departmentPharmaceutical Sciences
dc.relation.doihttps://doi.org/10.1111/acel.12550
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
dc.description.schoolcollegeLewis Katz School of Medicine
dc.description.schoolcollegeTemple University. School of Pharmacy
dc.creator.orcidBarrero|0000-0001-5779-6642
dc.creator.orcidMerali|0000-0002-0280-5289
dc.temple.creatorLi, Jian-Guo
dc.temple.creatorBarrero, Carlos
dc.temple.creatorMerali, Salim
dc.temple.creatorPractico, Domenico
refterms.dateFOA2023-03-07T20:01:16Z


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