dc.contributor.advisor | Shukla, Shivendra D. | eng |
dc.contributor.author | Choudhury, Mahua, 1977- | eng |
dc.date.issued | 2008 | eng |
dc.date.submitted | 2008 Summer | eng |
dc.description | The 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.description | Title from PDF of title page (University of Missouri--Columbia, viewed on April 6, 2010). | eng |
dc.description | Vita. | eng |
dc.description | Thesis advisor: Shivendra D. Shukla. | eng |
dc.description | "August 2008" | eng |
dc.description | Ph. D. University of Missouri-Columbia 2008. | eng |
dc.description.abstract | Although several mechanisms have identified for alcoholic liver disease, at present there are no precise mechanisms for liver injury. We have observed that surrogate alcohols increases histone H3 acetylation selectively at Lys 9 (H3AcK9) via metabolites in primary rat hepatocytes. Alcohols and metabolites both increased the HAT activity. However, propionate and butyrate also decreased HDAC activity. In addition, oxidative stress also mediates ethanol induced histone acetylation and ADH1 gene expression. It is likely that both NADPH oxidase and mitochondria derived ROS are involved. The study presented here also identifies for the first time the specific HAT, GCN5, responsible for ethanol induced H3AcK9 in human hepatoma cell overexpressing ADH1 (VA-13). siRNA knock down of GCN5 decreased both ethanol induced H3AcK9 and HAT activity. In summery, we conclude that ethanol increases H3AcK9 via modulation of GCN5 in the liver. These original findings may contribute to a better understanding of the mechanism underlying the pathogenesis of alcoholic liver disease. | eng |
dc.description.bibref | Includes bibliographical references. | eng |
dc.format.extent | xv, 181 pages | eng |
dc.identifier.oclc | 603557930 | eng |
dc.identifier.uri | https://hdl.handle.net/10355/6866 | |
dc.identifier.uri | https://doi.org/10.32469/10355/6866 | eng |
dc.language | English | eng |
dc.publisher | University of Missouri--Columbia | eng |
dc.relation.ispartofcommunity | University of Missouri--Columbia. Graduate School. Theses and Dissertations | eng |
dc.rights | OpenAccess. | eng |
dc.rights.license | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License. | |
dc.subject.lcsh | Alcoholic liver diseases | eng |
dc.subject.lcsh | Histones -- Metabolism | eng |
dc.subject.lcsh | Histones -- Effect of drugs on | eng |
dc.subject.lcsh | Acetyltransferases | eng |
dc.subject.lcsh | Alcohols -- Receptors -- Effect of drugs on | eng |
dc.subject.lcsh | Histone deacetylase -- Metabolism | eng |
dc.subject.mesh | Liver Diseases, Alcoholic -- etiology | eng |
dc.subject.mesh | Histones -- metabolism | eng |
dc.subject.mesh | Histones -- drug effects | eng |
dc.subject.mesh | Histone Acetyltransferases | eng |
dc.subject.mesh | Alcohols -- pharmacology | eng |
dc.subject.mesh | Histone Deacetylases -- metabolism | eng |
dc.title | Alcohol induced histone acetylation mediated by histone acetyl transferase GCN5 in liver | eng |
dc.type | Thesis | eng |
thesis.degree.discipline | Medical Pharmacology and Physiology (MU) | eng |
thesis.degree.grantor | University of Missouri--Columbia | eng |
thesis.degree.level | Doctoral | eng |
thesis.degree.name | Ph. D. | eng |