A5102859535- Pharmacogenetics and Drug Metabolism
- Vitamin D Research Studies
- Drug Transport and Resistance Mechanisms
- Estrogen and related hormone effects
- Carcinogens and Genotoxicity Assessment
- Protease and Inhibitor Mechanisms
- Toxic Organic Pollutants Impact
- Effects and risks of endocrine disrupting chemicals
- Biosensors and Analytical Detection
- Eicosanoids and Hypertension Pharmacology
- Retinoids in leukemia and cellular processes
- Advanced Biosensing Techniques and Applications
- Liver Disease Diagnosis and Treatment
- Hormonal Regulation and Hypertension
- Peroxisome Proliferator-Activated Receptors
- Endometriosis Research and Treatment
- Vitamin C and Antioxidants Research
- Genomics, phytochemicals, and oxidative stress
- Liver physiology and pathology
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cholesterol and Lipid Metabolism
- Blood Coagulation and Thrombosis Mechanisms
- Microfluidic and Capillary Electrophoresis Applications
- Metabolism and Genetic Disorders
- Garlic and Onion Studies
Nihon University
2010-2022
University of Cincinnati
2001-2013
University of Cincinnati Medical Center
2002-2013
University of Pennsylvania
2008
Kyoto City Hospital
1976-1977
The cytochrome P450 (CYP1A1) enzyme metabolically activates many polycyclic aromatic hydrocarbons, including benzo[<i>a</i>]pyrene (BaP), to DNA- and protein-binding intermediates that are associated with toxicity, mutagenesis, carcinogenesis. As a result, it is widely accepted CYP1A1 potentiates the toxicity of this class chemicals. In distinct contrast, we show here inducibility essential in detoxication oral BaP. We compared <i>Cyp1a1</i>(-/-) knockout mice, having genetic absence enzyme,...
CYP1A1 and CYP1B1 metabolically activate many polycyclic aromatic hydrocarbons (PAHs), including benzo[<i>a</i>]pyrene, to reactive intermediates associated with toxicity, mutagenesis, carcinogenesis. Paradoxically, however, <i>Cyp1a1</i><sup>-/-</sup> knockout mice are more sensitive oral benzo[<i>a</i>]pyrene exposure, compared wild-type <i>Cyp1a1</i><sup>+/+</sup> (<i>Mol Pharmacol</i><b>65:</b>1225, 2004). To further investigate the mechanism for this enhanced sensitivity,...
1alpha,25-Dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], a vitamin D receptor (VDR) ligand, regulates calcium homeostasis and also exhibits noncalcemic actions on immunity cell differentiation. In addition to disorders of bone metabolism, VDR ligands are potential therapeutic agents in the treatment immune disorders, microbial infections, malignancies. Hypercalcemia, major adverse effect derivatives, limits their clinical application. The secondary bile acid lithocholic (LCA) is an additional...
Benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon produced by cigarette combustion, is implicated as causative agent in smoking-related cancer and atherosclerosis. 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3], potent ligand for the nuclear receptor vitamin D (VDR), has been shown to decrease risk of osteoporosis, some types cardiovascular disease, suggesting an opposing effect smoking. In this study, we investigated effects BaP on signaling pathway. effectively enhanced 1,25(OH)2D3-dependent...
Vitamin D receptor (VDR), a nuclear that regulates calcium homeostasis, has been found to function as for secondary bile acids. Because the in vivo role of VDR acid metabolism remains unknown, we investigated effect activation mouse model cholestasis. We treated mice with 1alpha-hydroxyvitamin D(3) [1alpha(OH)D(3)] after duct ligation (BDL) and examined mRNA expression cytokine levels. 1alpha(OH)D(3) treatment altered genes involved synthesis transport liver, kidney, intestine but did not...
The vitamin D receptor (VDR) mediates the biological actions of 1,25-dihydroxyvitamin D<sub>3</sub> [1,25(OH)<sub>2</sub>D<sub>3</sub>], active form D, which regulates calcium homeostasis, immunity, cellular differentiation, and other physiological processes. We investigated effects three 1,25(OH)<sub>2</sub>D<sub>3</sub> derivatives on VDR function. AD47 has an adamantane ring LAC67a LAC67b have lactone substituents at side chain position. These bind to but do not stabilize cofactor...
Abstract Benzo[ a ]pyrene (BaP) is prototypical polycyclic aromatic hydrocarbon (PAH) found in combustion processes. Cytochrome P450 1A1 and 1B1 enzymes (CYP1A1 CYP1B1) can both detoxify PAHs activate them to cancer‐causing reactive intermediates. Following high dosage of oral BaP (125 mg/kg/day), ablation the mouse Cyp1a1 gene causes immunosuppression death within ∼28 days, whereas Cyp1 (+/+) wild‐type mice remain healthy for >12 months on this regimen. In study, male wild‐type, (−/−)...
Treating insulin resistance and type 2 diabetes in rodents, currently known retinoid X receptor (RXR) agonists induce significant adverse effects. Here we introduce a novel RXR partial agonist CBt-PMN (11b), which shows potent glucose-lowering effect improvements of secretion glucose tolerance without the serious effects caused by full agonists. We suggest that may be new class antitype drug candidates.
Benzo[<i>a</i>]pyrene (BaP) activates the aryl hydrocarbon (AHR) and induces expression of genes involved in xenobiotic metabolism, including CYP1A1. CYP1A1 is not only BaP detoxification but also metabolic activation, which results DNA adduct formation. Vitamin D receptor (VDR) belongs to NR1I subfamily nuclear superfamily, regulates metabolism genes. We investigated cross-talk between AHR VDR signaling pathways found that 1α,25-dihydroxyvitamin D<sub>3</sub>...
In the past, CYP1A1 protein was known to be located in endoplasmic reticulum (ER; microsomes). More recently, shown also targeted inner mitochondrial membrane; import is dependent on NH<sub>2</sub>-terminal processing that exposes a cryptic targeting signal. It interesting microsomal and enzymes exhibit different substrate specificities, electron donors, inducer properties. To understand physiological functions of versus CYP1A1, we have generated three knock-in lines by altering...
The liver X receptor α (LXRα) is a nuclear that involved in regulation of lipid metabolism, cellular proliferation and apoptosis, immunity. In this report, we characterize three human LXRα isoforms with variation the ligand-binding domain (LBD). While examining expression LXRα3, which lacks 60 amino acids within LBD, identified two novel transcripts encode LXRα-LBD variants (LXRα4 LXRα5). LXRα4 has an insertion 64 helix 4/5, LXRα5 C-terminal helices 7 to 12 due termination codon additional...
Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon found in cigarette smoke, grilled meats and byproducts of industrial incineration. BaP exposure through smoking has been implicated the pathogenesis lung head-and-neck cancers atherosclerosis. inhalation activates aryl receptor (AHR), transcription factor that induces expression genes involved xenobiotic metabolism. can be metabolized to active compounds form DNA adducts induce production reactive oxygen species cells, leading...
The human ether à go-go 1 potassium channel (hEAG1) is required for cell cycle progression and proliferation of cancer cells. Inhibitors hEAG1 activity expression represent potential therapeutic drugs in cancer. Previously, we have shown that downregulated by calcitriol a variety Herein, provided evidence on the regulatory mechanism involved such repressive effect cells derived from cervical Our results indicate repression occurs at transcriptional level involves functional negative vitamin...