A5032620184- Drug Transport and Resistance Mechanisms
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Pharmacogenetics and Drug Metabolism
- RNA modifications and cancer
- Liver Disease Diagnosis and Treatment
- Aldose Reductase and Taurine
- Cholesterol and Lipid Metabolism
- Glutathione Transferases and Polymorphisms
- Folate and B Vitamins Research
- Genetics and Neurodevelopmental Disorders
- Attention Deficit Hyperactivity Disorder
- Nutrition, Genetics, and Disease
- Computational Drug Discovery Methods
- Adenosine and Purinergic Signaling
- Drug-Induced Hepatotoxicity and Protection
- Genomics, phytochemicals, and oxidative stress
- Prenatal Substance Exposure Effects
- Birth, Development, and Health
- Pharmacology and Obesity Treatment
- Autism Spectrum Disorder Research
- Sirtuins and Resveratrol in Medicine
- Inflammatory mediators and NSAID effects
- Genomics and Chromatin Dynamics
- Biochemical effects in animals
Northern Great Plains Research Laboratory
2014-2019
University of Kansas Medical Center
2011-2016
University of Michigan
2006-2014
University of Kansas
2012
The 274 tRNA genes in Saccharomyces cerevisiae are scattered throughout the linear maps of 16 chromosomes, but clustered at nucleolus when compacted nucleus. This clustering is dependent on intact nucleolar organization and contributes to gene-mediated (tgm) silencing RNA polymerase II transcription near genes. After examination localization mechanism, we find that chromosome-condensing complex, condensin, involved Conditionally defective mutations all five subunits which confirm bound...
Although the ability of disulfiram to inactivate CYP2E1 has been known for more than 20 years, mechanism not yet elucidated. A metabolite disulfiram, diethyldithocarbamate (DDC), is converted by a reactive intermediate that subsequently inactivates protein, leading mechanism-based inactivation. Mass spectral analysis inactivated human 2E1 protein demonstrates inactivation due formation an adduct DDC with apoprotein. These data, along mass trapped GSH, indicate involvement molecular 116 Da....
Significance This study provides new insight into the requirements for observed silencing of RNA polymerase II transcription near tRNA genes. Mod5 is a conserved modification enzyme found in both nucleus and cytoplasm, although it only modifies tRNAs cytoplasm. required genes, bound to nuclear gene complexes pre-tRNA transcripts. Possible mechanisms this form RNA-mediated transcriptional are discussed.
Aldo-keto reductases (Akrs) are a conserved group of NADPH-dependent oxido-reductase enzymes. This study provides comprehensive examination the tissue distribution 16 substrate-metabolizing Akrs in mice, their expression during development, and whether they altered by chemicals that activate distinct transcriptional factor pathways. Akr1c6, 1c14, 1c20, 1c22 primarily present liver; Akr1a4, 1c18, 1c21, 7a5 kidney; Akr1d1 liver Akr1b7 small intestine; Akr1b3 Akr1e1 brain; Akr1b8 testes;...
The endocannabinoid system plays an important role in numerous physiological processes including mood, appetite, and pain sensation. A critical compound maintaining cannabinoid tone is the anandamide (AEA). We have recently shown that AEA metabolized by several different human cytochromes P450 (P450) to form a number of metabolites, one which exhibits increased biological activity. CYP3A4, major P450s involved metabolism AEA, produces four metabolites. One these 5,6-epoxyeicosatrienoic acid...
Activation of Constitutive Androstane Receptor (CAR) protects against bile acid (BA)-induced liver injury. This study was performed to determine the effect CAR activation on flow, BA profile, as well expression synthesis and transport genes. Synthetic ligand 1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) administered mice for 4 days. BAs were quantified by UPLC-MS/MS (ultraperformance liquid chromatography-tandem mass spectrometry). decreases total in livers male (49%) female (26%),...
We examined the effects of two over-the-counter H1-antihistamines on progression fatty liver disease in male C57Bl/6 wild-type and apolipoprotein E (ApoE)-/- mice. Mice were fed a high-fat diet (HFD) for 3 mo, together with administration either cetirizine (4 mg/kg body wt) or fexofenadine (40 drinking water. Antihistamine treatments increased weight gain, gonadal fat deposition, weight, hepatic steatosis mice but not ApoE-/- Lobular inflammation, acute necrosis affected by genotype. Serum...
The mechanism-based inactivation of human CYP2B6 by <i>tert</i>-butylphenylacetylene (BPA) in the reconstituted system was investigated. BPA is time-, concentration-, and NADPH-dependent exhibits a <i>K</i><sub>I</sub> 2.8 μM, <i>k</i><sub>inact</sub> 0.7 min<sup>−1</sup>, <i>t</i><sub>1/2</sub> 1 min. partition ratio ∼5. Unlike CYP2B1 CYP2B4, addition to formation an apoprotein adduct glutathione conjugate, small heme observed when incubated with BPA. mass increase adducted GSH conjugate...
Transfer RNA genes are distributed throughout eukaryotic genomes, and frequently found as multicopy families. In Saccharomyces cerevisiae, tRNA gene transcription by polymerase III suppresses nearby II, partially because the clustered near nucleolus. We have tested whether active of might also suppress recombination, since recombination between identical copies repetitive could delete intervening be detrimental to survival. The opposite proved case. Recombination was elevated, but only when...
Studies in microsomal and reconstituted systems have shown that the presence of one cytochrome P450 isoform can significantly influence catalytic activity another isoform. In this study, we assessed whether CYP2E1 could CYP2B4 under steady-state turnover conditions. The results show inhibits CYP2B4-mediated metabolism benzphetamine (BNZ) with a <i>K</i><sub>i</sub> 0.04 µM. However, is not an inhibitor CYP2E1-mediated <i>p-</i>nitrophenol hydroxylation. When these inhibition studies were...