The epitranscriptomic writer ALKBH8 drives tolerance and protects mouse lungs from the environmental pollutant naphthalene.

Autor:	Leonardi A; Department of Nanoscale Science and Engineering, University at Albany , Albany, NY, USA., Kovalchuk N; College of Pharmacy, Department of Toxicology and Pharmacology, University of Arizona , Tucson, AZ, USA., Yin L; College of Pharmacy, Department of Toxicology and Pharmacology, University of Arizona , Tucson, AZ, USA., Endres L; College of Arts and Sciences, SUNY Polytechnic Institute , Utica, NY, USA.; The RNA Institute, University at Albany , Albany, NY, USA., Evke S; Nanoscale Science Constellation, SUNY Polytechnic Institute , Albany, NY, USA., Nevins S; Nanoscale Science Constellation, SUNY Polytechnic Institute , Albany, NY, USA., Martin S; Department of Biological Sciences, University at Albany , Albany, NY, USA., Dedon PC; Department of Biological Engineering, Massachusetts Institute of Technology , Cambridge, MA, USA.; Antimicrobial Resistance Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology , Singapore., Melendez JA; The RNA Institute, University at Albany , Albany, NY, USA.; Nanoscale Science Constellation, SUNY Polytechnic Institute , Albany, NY, USA., Van Winkle L; Center for Health and the Environment, University of California Davis , Davis, CA, USA., Zhang QY; College of Pharmacy, Department of Toxicology and Pharmacology, University of Arizona , Tucson, AZ, USA., Ding X; College of Pharmacy, Department of Toxicology and Pharmacology, University of Arizona , Tucson, AZ, USA., Begley TJ; The RNA Institute, University at Albany , Albany, NY, USA.; Department of Biological Sciences, University at Albany , Albany, NY, USA.
Jazyk:	angličtina
Zdroj:	Epigenetics [Epigenetics] 2020 Oct; Vol. 15 (10), pp. 1121-1138. Date of Electronic Publication: 2020 Apr 17.
DOI:	10.1080/15592294.2020.1750213
Abstrakt:	The 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 ( Alkbh8 def ) 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), Alkbh8 de f and Cyp2abfgs-null mice, the latter of which lack the cytochrome P450 enzymes required for naphthalene bioactivation. Under basal conditions, lungs from Alkbh8 def mice have increased markers of oxidative stress and decreased thioredoxin reductase protein levels, and have reprogrammed gene expression to differentially regulate stress response transcripts. Alkbh8 def 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 Alkbh8 def 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 .
Databáze:	MEDLINE
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