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dc.contributor.advisorShukla, Shivendra D.eng
dc.contributor.authorJames, Taryneng
dc.date.issued2011eng
dc.date.submitted2011 Summereng
dc.descriptionTitle from PDF of title page (University of Missouri--Columbia, viewed on May 21, 2012).eng
dc.descriptionThe entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file.eng
dc.descriptionDissertation advisor: Dr. Shivendra D. Shuklaeng
dc.descriptionVita.eng
dc.description"July 2011"eng
dc.description.abstractEpigenetic histone modification is emerging as a critical player in the cellular actions of ethanol. In this context, we administered ethanol intraperitoneally to rats, to mimic binge drinking in humans. A dose response and time course experiments revealed that histone H3 phosphorylation and phosphoacetylation increases in vivo in liver. H3 serine 28 phosphorylation was more sensitive than serine-10 to low dose of ethanol, 1.75 g/Kg, but both were not observed at 5 g/Kg. In contrast, phosphoacetylation was observed at 5 g/Kg. There was a biphasic response in phosphorylation of both serines with time while phosphoacetylation increased rapidly at the highest time point (4h). Phosphorylation of JNK, p38, and ERK MAP kinases increased along with liver injury i.e. apoptosis, necrosis, and steatosis. The mRNA expression of genes (i.e. c-Fos, c-Jun, MKP-1, LDL-r, TNF and PAI-1) that play role in alcoholic liver injury, were also modulated. ChIP assays revealed differential association of site specific phosphorylation and phosphoacetylation with gene promoters, i.e. serine 10 phosphorylation with c-Fos and c-Jun; serine 28 phosphorylation with c-Jun, and PAI-1; and K9/S10 phosphoacetylation with PAI-1. We demonstrate for the first time that ethanol binge induction of histone H3 phosphorylation and phosphoacetylation in vivo in liver are associated with the promoters of genes. Taken together, these data are relevant to the identification of “early” molecular processes involved in the binge induced liver injury.eng
dc.format.extentxv, 219 pageseng
dc.identifier.oclc872560759eng
dc.identifier.urihttps://doi.org/10.32469/10355/14289eng
dc.identifier.urihttps://hdl.handle.net/10355/14289
dc.languageEnglisheng
dc.publisherUniversity of Missouri--Columbiaeng
dc.relation.ispartofcollectionUniversity of Missouri--Columbia. Graduate School. Theses and Dissertations.eng
dc.rightsOpenAccess.eng
dc.rights.licenseThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License.
dc.subjectepigeneticseng
dc.subjectethanoleng
dc.subjecthistone modificationeng
dc.subjectbinge drinkingeng
dc.titleHistone H3 phosphorylation and phosphoacetylation in the liver of rats treated in vivo with acute ethanoleng
dc.typeThesiseng
thesis.degree.disciplinePharmacology (MU)eng
thesis.degree.grantorUniversity of Missouri--Columbiaeng
thesis.degree.levelDoctoraleng
thesis.degree.namePh. D.eng


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