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Epigenetics of proteasome inhibition in the liver of rats fed ethanol chronically

World Journal of Gastroenterology 2009年第6期15卷 705-712页

作者： joan oliva Jennifer Dedes Samuel W French Fawzia Bardag-Gorce Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center TorranceCA 90502 United States

AIM： TO examine the effects of ethanol-induced proteasome inhibition, and the effects of proteasome inhibition in the regulation of epigenetic mechanisms.METHODS： Rats were fed ethanol for 1 mo using the Tsukamoto-French model and were compared to rats given the proteasome inhibitor PS-341 （Bortezomib, Velcade^TM） by intraperitoneal injection. Microarray analysis and real time PCR were performed and proteasome activity assays and Western blot analysis were performed using isolated nuclei.RESULTS： Chronic ethanol feeding caused a significant inhibition of the ubiquitin proteasome pathway in the nucleus, which led to changes in the turnover of transcriptional factors, histone-modifying enzymes, and, therefore, affected epigenetic mechanisms. Chronic ethanol feeding was related to an increase in histone acetylation, and it is hypothesized that the proteasome proteolytic activity regulated histone modifications by controlling the stability of histone modifying enzymes, and, therefore, regulated the chromatin structure, allowing easy access to chromatin by RNA polymerase, and, thus, proper gene expression. Proteasome inhibition by PS-341 increased histone acetylation similar to chronic ethanol feeding. In addition, proteasome inhibition caused dramatic changes in hepatic remethylation reactions as there was a significant decrease in the enzymes responsible for the regeneration of S-adenosylmethionine, and, in particular, a significant decrease in the betaine-homocysteine methyltransferase enzyme. This suggested that hypomethylation was associated with proteasome inhibition, as indicated by the decrease in histone methylation.CONCLUSION： The role of proteasome inhibition in regulating epigenetic mechanisms, and its link to liver injury in alcoholic liver disease, is thus a promising approach to study liver injury due to chronic ethanol consumption.

关键词： Alcohol liver injury Betaine Epigenetic mechanisms Homocysteine methyltransferase Proteasome inhibition S-adenosylmethionine

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Alcohol,nutrition and liver cancer:Role of Toll-like receptor signaling

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World Journal of Gastroenterology 2010年第11期16卷 1344-1348页

作者： Samuel W French joan oliva Barbara A French Fawzia Bardag-Gorce Department of Pathology Harbor-UCLA Medical Center

This article reviews the evidence that ties the development of hepatocellular carcinoma (HCC) to the natural immune pro-inflammatory response to chronic liver disease, with a focus on the role of Toll-like receptor (TLR) signaling as the mechanism of liver stem cell/progenitor transformation to HCC. Two exemplary models of this phenomenon are reviewed in detail. One model applies chronic ethanol/lipopolysaccharide feeding to the activated TLR4 signaling pathway. The other applies chronic feeding of a carcinogenic drug, in which TLR2 and 4 signaling pathways are activated. In the drug-induced model, two major methyl donors, S-adenosylmethionine and betaine, prevent the upregulation of the TLR signaling pathways and abrogate the stem cell/progenitor proliferation response when fed with the carcinogenic drug. This observation supports a nutritional approach to liver cancer prevention and treatment. The observation that upregulation of the TLR signaling pathways leads to liver tumor formation gives evidence to the popular concept that the chronic pro-inflammatory response is an important mechanism of liver oncogenesis. It provides a nutritional approach, which could prevent HCC from developing in many chronic liver diseases.

关键词： Toll-like receptor Hepatocellular carcinoma Methyl donors, Epigenetic processes Inflammation Alcohol Drug toxicity Lipopolysaccharides

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Mallory-Denk body pathogenesis revisited

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World Journal of Hepatology 2010年第8期2卷 295-301页

作者： Samuel W French Fawzia Bardag-Gorce Barbara A French joan oliva Department of Pathology Harbor-UCLA Medical Center

This editorial reviews the recent evidence showing that Mallory-Denk bodies(MDBs)form in hepatocytes as the result of a drug-induced shift from the 26s proteasome formation to the immunoproteasome *** shift is the result of changes in gene expression induced in promoter activation,which is induced by the IFNγ and TNFa signaling *** activates TLR 2 and 4 *** TLR signaling pathway stimulates both the induction of a cytokine proinflammatory response and an up regulation of growth *** MDB-forming hepatocytes proliferate as a result of the increase in growth factor expression by the MDBforming cells,which selectively proliferate in response to drug *** of these mechanisms are induced by drug toxicity,and are prevented by feeding the methyl donors SAMe and betaine,supporting the epigenetic response of MDB formation.

关键词： Toll-like receptor Proinflammatory Methyl donors Epigenetic processes Drug toxicity 26s Proteasome Immunoproteasome

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Luminescent Properties of the Mn<sup>2+</sup>Ion in Zinc Phosphate Glass

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Open Journal of Applied Sciences 2021年第11期11卷 1212-1217页

作者： Frida Lissete Flores Rivera Dulce Yolotzin Medina Velazquez Gabriela Verenice Arredondo Martínez Jorge Roberto oliva Uc Carlos Eduardo Rodriguez Garcia Miguel Angel Barron-Meza joan Reyes Miranda Autonomus Metropolitan University Material Area Mexico City Mexico Potosino Institute for Scientific and Technological Research Advanced Materials Division San Luis Mexico Faculty of Physics-Mathematics Autonomous University of Coahuila Saltillo Mexico

In the development of new optoelectronic devices, mainly those related to solid state technology (SSL), the generation of luminescent materials with high intensity in visible region and low cost is of vital importance. For this reason, this work presents the luminescent properties of zinc phosphate glasses doped with the manganese ion 2+. The manganese ion offers a series of advantages with respect to rare earths, such as a more accessible cost and an intense emission in the red color that make it a great candidate for the generation of new optoelectronic devices. The methodology for the synthesis is presented in this work, as well as its luminescent properties, for concentrations of 2%, 10%, 13% and 15% atomic.

关键词： Luminescence Manganese Advanced Glasses

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