A5040073148- Pharmacogenetics and Drug Metabolism
- Drug Transport and Resistance Mechanisms
- Estrogen and related hormone effects
- Hormonal Regulation and Hypertension
- Receptor Mechanisms and Signaling
- RNA Interference and Gene Delivery
- Computational Drug Discovery Methods
- Eicosanoids and Hypertension Pharmacology
- Advanced biosensing and bioanalysis techniques
- Virus-based gene therapy research
- Retinoids in leukemia and cellular processes
- Hormonal and reproductive studies
- Steroid Chemistry and Biochemistry
- Inflammatory mediators and NSAID effects
- Analytical Chemistry and Chromatography
- Effects and risks of endocrine disrupting chemicals
- Retinal Diseases and Treatments
- Drug-Induced Hepatotoxicity and Protection
- Cholinesterase and Neurodegenerative Diseases
- Metabolism and Genetic Disorders
- Alcohol Consumption and Health Effects
- Pharmacological Effects and Assays
- DNA and Nucleic Acid Chemistry
- Pharmacological Effects and Toxicity Studies
- Liver physiology and pathology
University of Eastern Finland
2015-2024
University of North Carolina at Chapel Hill
2019-2024
University of Helsinki
2022
Universidade de Santiago de Compostela
2022
Center for Research in Molecular Medicine and Chronic Diseases
2022
Instituto de Investigación Sanitaria de Santiago
2022
Machida Endoscope (Japan)
2022
Finland University
2008-2022
Uppsala University
2021
University of Maryland, Baltimore
2021
ABSTRACTPBREM, the phenobarbital-responsive enhancer module of cytochrome P-450 Cyp2b10 gene, contains two potential nuclear receptor binding sites, NR1 and NR2. Consistent with finding that anti-retinoid X (RXR) could supershift NR1-nuclear protein complex, DNA affinity chromatography oligonucleotides enriched orphan RXR from hepatic extracts phenobarbital-treated mice. In addition to RXR, CAR was present in same fraction. mice, both rapidly increased before induction CYP2B10 mRNA....
The endogenous CYP2B6 gene becomes phenobarbital (PB) inducible in androstenol-treated HepG2 cells either transiently or stably transfected with a nuclear receptor CAR expression vector. PB induction mediated by is regulated conserved 51-base pair element called PB-responsive enhancer module (PBREM) that has now been located between −1733 and −1683 bp the gene's 5′-flanking region. An vitro translated acting as retinoid X α heterodimer binds directly to two sites NR1 NR2 within PBREM. In...
Members of the nuclear-receptor superfamily mediate crucial physiological functions by regulating synthesis their target genes. Nuclear receptors are usually activated ligand binding. Cytochrome P450 (CYP) isoforms often catalyse both formation and degradation these ligands. CYPs also metabolize many exogenous compounds, some which may act as activators nuclear disruptors endocrine cellular homoeostasis. This review summarizes recent findings that indicate major classes CYP genes selectively...
It has been shown that extracellular glycosaminoglycans (GAGs) limit the gene transfer by cationic lipids and polymers. The purpose of this study was to clarify how interactions with anionic GAGs (hyaluronic acid heparan sulfate) modify cellular uptake distribution lipoplexes polyplexes. Experiments on DNA GFP reporter expression showed decreased can rarely be explained lower uptake. In most cases, is not changed GAG binding or Reporter blocked sulfate, but it increased hyaluronic acid;...
By extending previous studies of the phenobarbital (PB)-responsive 132-base pair (bp) enhancer sequence in <i>CYP2B10</i>gene, we have delimited a 51-bp element that is fully inducible by PB mouse primary hepatocytes. Sixteen structurally unrelated phenobarbital-type inducers activated transient transfection assays. The results thus indicate most PB-type inducers, if not all increase transcription <i>CYP2B10</i> gene activating this element, now designated PB-responsive module or PBREM.
Abstract We undertook this study to answer several questions regarding nitrosamine metabolism. Kinetics of metabolism showed the involvement at least two enzymes in dealkylation N ‐nitrosodiethylamine (NDEA) and ‐nitrosodimethylamine (NDMA) mouse liver microsomes. Coumarin inhibited both reactions competitively. On other hand, microsomal coumarin 7‐hydroxylase was by NDMA ( K i 2.7 mM) NDEA 0.013 mM). The big difference values suggests a higher affinity than Cyp2a‐5 (mouse cytochrome P450...
Induction of drug- and carcinogen-metabolizing cytochrome P450s by xenobiotic chemicals is a common cellular defense mechanism, usually leading to increased detoxification xenobiotics but sometimes, paradoxically, formation more toxic carcinogenic metabolites. Phenobarbital (PB) an archetypal representative for including industrial solvents, pesticides, plant products, clinically used drugs that induce several genes within CYP subfamilies 2B, 2A, 2C, 3A in rodents humans. Although the...
Abstract Degeneration of retinal pigment epithelial (RPE) cells is a clinical hallmark age-related macular degeneration (AMD), the leading cause blindness among aged people in Western world. Both inflammation and oxidative stress are known to play vital roles development this disease. Here, we assess ability fisetin luteolin, protect ARPE-19 from stress-induced cell death decrease intracellular inflammation. We also compare growth reactivity human serum-free serum-containing conditions. The...
Abstract Background Cationic polymers and liposomes are used to wrap DNA into complexes that promote its cellular uptake. The mechanisms of the uptake intracellular fate these obscure, as reasons for an unpredictable sometimes poor efficiency transgene expression. Polyanionic glycosaminoglycans (GAGs) on cell surface interact with cationic influence transfection. Methods quantities heparan sulfate (HS), chondroitin (CS) hyaluronan (HA) mutated Chinese hamster ovary (CHO) cells manipulated...
The mouse phenobarbital (PB)-inducible Cyp2b10 gene promoter has been isolated and sequenced, control of its expression characterized. 1405-base pair (bp) sequence is 83% identical to the corresponding region from rat CYP2B2 gene. In addition lack CA repeats, differences include insertion 42 base pairs (−123/-82 bp) into middle a consensus so-called “Barbie box.” this report, we have developed primary hepatocyte culture system in which endogenous 2B10 mRNA as well Cyp2b10-driven CAT activity...
Using a primary hepatocyte culture in which the mouse Cyp2b10 gene transcription is activated by phenobarbital (PB)-type inducers, we examined cellular signalling mechanisms associated with PB induction. Low nanomolar concentrations of protein serine/threonine phosphatase inhibitors okadaic acid (OA) and calyculin A blocked induction CYP2B10 mRNA. Nuclear run-on assays indicated that OA suppressed transcription. Pretreatment cells an inhibitor Ca2+/calmodulin-dependent kinases...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMouse steroid 15.alpha.-hydroxylase gene family: identification of type II P-45015.alpha. as coumarin 7-hydroxylaseMasahiko Negishi, Raija Lindberg, Barbara Burkhart, Takeshi Ichikawa, Paavo Honkakoski, and Matti LangCite this: Biochemistry 1989, 28, 10, 4169–4172Publication Date (Print):May 16, 1989Publication History Published online1 May 2002Published inissue 16 1989https://doi.org/10.1021/bi00436a007RIGHTS & PERMISSIONSArticle...
Exposure to metabolism-disrupting chemicals, which are a specific type of endocrine-disrupting chemical (EDC), is linked metabolic problems such as dyslipidemia, insulin resistance, and hepatic steatosis. Steroid hormone receptors (SHRs) within the nuclear receptor superfamily well-known targets for EDCs in reproductive tissues and, lesser extent, liver. In this study, we investigated how five well-established SHR ligands eight including pesticides, plasticizers, pharmaceuticals, flame...
Exposure to metabolism-disrupting chemicals (MDCs), compounds largely belonging the group of endocrine-disrupting (EDCs), is associated with metabolic dysfunctions such as dyslipidemia, insulin resistance and hepatic steatosis. Steroid hormone receptors (SHRs) are known targets for MDCs but their regulatory environment in presence environmental remains elusive. Here, we studied activation molecular interactions SHRs exposed 17 suspected including pesticides, plasticizers, pharmaceuticals,...