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Full-Text Articles in Pharmacy and Pharmaceutical Sciences

Fxr Acetylation Is Normally Dynamically Regulated By P300 And Sirt1 But Constitutively Elevated In Metabolic Disease States, Jongsook Kim Kemper, Zhen Xiao, Bhaskar Ponugoti, Ji Miao, Sungsoon Fang, Deepthi Kanamaluru, Stephanie Tsang, Shwu-Yuan Wu, Cheng-Ming Chiang, Timothy D. Veenstra Nov 2009

Fxr Acetylation Is Normally Dynamically Regulated By P300 And Sirt1 But Constitutively Elevated In Metabolic Disease States, Jongsook Kim Kemper, Zhen Xiao, Bhaskar Ponugoti, Ji Miao, Sungsoon Fang, Deepthi Kanamaluru, Stephanie Tsang, Shwu-Yuan Wu, Cheng-Ming Chiang, Timothy D. Veenstra

Pharmaceutical Sciences Faculty Publications

The nuclear bile acid receptor FXR is critical for regulation of lipid and glucose metabolism. Here, we report that FXR is a target of SIRT1, a deacetylase that mediates nutritional and hormonal modulation of hepatic metabolism. Lysine 217 of FXR is the major acetylation site targeted by p300 and SIRT1. Acetylation of FXR increases its stability but inhibits heterodimerization with RXRalpha, DNA binding, and transactivation activity. Downregulation of hepatic SIRT1 increased FXR acetylation with deleterious metabolic outcomes. Surprisingly, in mouse models of metabolic disease, FXR interaction with SIRT1 and p300 was dramatically altered, FXR acetylation levels were elevated, and overexpression …


Using A Global Proteomic Approach To Identify Proteins Affected By Estrogen Therapy, Timothy D. Veenstra Jun 2009

Using A Global Proteomic Approach To Identify Proteins Affected By Estrogen Therapy, Timothy D. Veenstra

Pharmaceutical Sciences Faculty Publications

With the increase in technological capabilities for measuring biological molecules, there is a greater trend to conduct non-biased, discovery-driven studies that collect information on hundreds of molecules in a single study. The hope is that novel findings can be detected within these large datasets. For protein analysis, these non-biased studies are particularly challenging as no technology is presently capable of providing a view of the entire proteome. The ability of non-biased studies to accurately detect specific differences within the proteomes of samples obtained from differentially treated individuals must be conclusively demonstrated before investigators will routinely adopt these methods as part …


How Close Is The Bench To The Bedside? Metabolic Profiling In Cancer Research, Que N. Van, Timothy D. Veenstra Jan 2009

How Close Is The Bench To The Bedside? Metabolic Profiling In Cancer Research, Que N. Van, Timothy D. Veenstra

Pharmaceutical Sciences Faculty Publications

Metabolic profiling using mass spectrometry (MS) and nuclear magnetic resonance spectroscopy (NMR) is integral to the rapidly expanding field of metabolomics, which is making progress in toxicology, plant science and various diseases, including cancer. In the area of oncology and metabolic phenotyping, researchers have probed the known changes in malignant cellular pathways using new experimental techniques to gain more insights, and others are exploiting these same cellular pathways for therapeutic drug targets and for novel cancer biomarkers, with the ultimate goal of translation to the clinic. Here, we discuss the challenges and opportunities in metabolic phenotyping for discovering novel cancer …


Brugia Malayi Excreted/Secreted Proteins At The Host/Parasite Interface: Stage- And Gender-Specific Proteomic Profiling, Sasisekhar Bennuru, Roshanak Semnani, Zhaojing Meng, Jose M.C. Ribeiro, Timothy D. Veenstra, Thomas B. Nutman Jan 2009

Brugia Malayi Excreted/Secreted Proteins At The Host/Parasite Interface: Stage- And Gender-Specific Proteomic Profiling, Sasisekhar Bennuru, Roshanak Semnani, Zhaojing Meng, Jose M.C. Ribeiro, Timothy D. Veenstra, Thomas B. Nutman

Pharmaceutical Sciences Faculty Publications

Relatively little is known about the filarial proteins that interact with the human host. Although the filarial genome has recently been completed, protein profiles have been limited to only a few recombinants or purified proteins of interest. Here, we describe a large-scale proteomic analysis using microcapillary reverse-phase liquid chromatography-tandem-mass spectrometry to identify the excretory-secretory (ES) products of the L3, L3 to L4 molting ES, adult male, adult female, and microfilarial stages of the filarial parasite Brugia malayi. The analysis of the ES products from adult male, adult female, microfilariae (Mf), L3, and molting L3 larvae identified 852 proteins. Annotation suggests …