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dc.contributor.authorLeonardi, Andrea
dc.contributor.authorKovalchuk, Nataliia
dc.contributor.authorYin, Lei
dc.contributor.authorEndres, Lauren
dc.contributor.authorEvke, Sara
dc.contributor.authorNevins, Steven
dc.contributor.authorMartin, Samuel
dc.contributor.authorDedon, Peter C.
dc.contributor.authorMelendez, J. Andres
dc.contributor.authorVan Winkle, Laura
dc.contributor.authorZhang, Qing-Yu
dc.contributor.authorDing, Xinxin
dc.contributor.authorBegley, Thomas J
dc.date.accessioned2020-06-22T13:53:11Z
dc.date.available2020-06-22T13:53:11Z
dc.date.issued2020-04
dc.date.submitted2019-12
dc.identifier.issn1559-2294
dc.identifier.issn1559-2308
dc.identifier.urihttps://hdl.handle.net/1721.1/125909
dc.description.abstractThe epitranscriptomic writer Alkylation Repair Homolog 8 (ALKBH8) is a transfer RNA (tRNA) methyltransferase that modifies the wobble uridine of selenocysteine tRNA to promote the specialized translation of selenoproteins. Using Alkbh8 deficient (Alkbh8def) mice, we have investigated the importance of epitranscriptomic systems in the response to naphthalene, an abundant polycyclic aromatic hydrocarbon and environmental toxicant. We performed basal lung analysis and naphthalene exposure studies using wild type (WT), Alkbh8def and Cyp2abfgs-null mice, the latter of which lack the cytochrome P450 enzymes required for naphthalene bioactivation. Under basal conditions, lungs from Alkbh8def mice have increased markers of oxidative stress and decreased thioredoxin reductase protein levels, and have reprogrammed gene expression to differentially regulate stress response transcripts. Alkbh8def mice are more sensitive to naphthalene induced death than WT, showing higher susceptibility to lung damage at the cellular and molecular levels. Further, WT mice develop a tolerance to naphthalene after 3 days, defined as resistance to a high challenging dose after repeated exposures, which is absent in Alkbh8def mice. We conclude that the epitranscriptomic writer ALKBH8 plays a protective role against naphthalene-induced lung dysfunction and promotes naphthalene tolerance. Our work provides an early example of how epitranscriptomic systems can regulate the response to environmental stress in vivo.en_US
dc.description.sponsorshipNational Institute of Environmental Health Sciences (Grant R01ES020867)en_US
dc.description.sponsorshipNational Institutes of Health (Grant P30ES006694)en_US
dc.description.sponsorshipNational Institutes of Health (Grant R01ES024615)en_US
dc.publisherInforma UK Limiteden_US
dc.relation.isversionofhttp://dx.doi.org/10.1080/15592294.2020.1750213en_US
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourceJosephina Leeen_US
dc.titleThe epitranscriptomic writer ALKBH8 drives tolerance and protects mouse lungs from the environmental pollutant naphthaleneen_US
dc.typeArticleen_US
dc.identifier.citationLeonardi, Andrea et al. "The epitranscriptomic writer ALKBH8 drives tolerance and protects mouse lungs from the environmental pollutant naphthalene." Epigenetics (April 2020) © 2020 The Author(s)en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Center for Environmental Health Sciencesen_US
dc.relation.journalEpigeneticsen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.date.submission2020-06-17T21:47:00Z
mit.licensePUBLISHER_CC


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