Search results for "P3"

Genetics of the variable expression of CYP3A in humans.

2004

CYP3A isozymes participate in the metabolism of 45-60% of currently used drugs and of a variety of other compounds such as steroid hormones, toxins, and carcinogens. The CYP3A expression status is a major determinant of drug efficacy and safety, and it may also affect an individual's predisposition to certain cancers. The inter- and intraindividual expression of CYP3A is variable because of a complex interplay between genetic and environmental factors. Markers predictive of the individual CYP3A activity could improve therapies with CYP3A substrates by personalised dose adjustments, but their development has been slower than for other drug-metabolizing enzymes. Here we summarize the recent p…

CYP3A5*3 and CYP2C8*3 variants influence exposure and clinical outcomes of tacrolimus-based therapy

2020

Aim: The influence of variants in pharmacokinetics-related genes on long-term exposure to tacrolimus (TAC)-based therapy and clinical outcomes was investigated. Patients & methods: Brazilian kidney recipients were treated with TAC combined with everolimus (n = 178) or mycophenolate sodium (n = 97). The variants in CYP2C8, CYP2J2, CYP3A4, CYP3A5, POR, ABCB1, ABCC2, ABCG2, SLCO1B1 and SLCO2B1 were analyzed. Main results: CYP3A5*3/*3 genotype influenced increase in TAC concentration from week 1 to month 6 post-transplantation (p < 0.05). The living donor and CYP2C8*3 variant were associated with reduced risk for delayed graft function (OR = 0.07; 95% CI = 0.03–0.18 and OR = 0.45; 95% C…

Shikonin reduces oedema induced by phorbol ester by interfering with IκBα degradation thus inhibiting translocation of NF-κB to the nucleus

2010

Background and purpose In the present paper we studied the effect of shikonin on ear oedema induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), and determined the mechanisms through which shikonin might exert its topical anti-inflammatory action. Experimental approach Acute ear oedema was induced in mice by topical application of TPA. The in vitro assays used macrophages RAW 264.7 cells stimulated with lipopolysaccharide. Cyclooxygenase-2, inducible nitric oxide synthase, protein kinase Calpha, extracellular signal-regulated protein kinase (ERK), phosphorylated ERK (pERK), c-Jun N-terminal kinase (JNK), pJNK, p38, p-p38, p65, p-p65, inhibitor protein of nuclear factor-kappaB (NF-kappaB) …

Transcriptional regulation and expression of CYP3A4 in hepatocytes.

2007

CYP3A4 is the most abundantly expressed drug-metabolizing P450 enzyme in human liver and contributes to the metabolism of a large number of drugs in use today. CYP3A4 is constitutively expressed in adult hepatocytes but it can also be transcriptionally induced by a variety of structurally diverse xenochemicals. CYP3A4 strongly contributes to the important variability in the therapeutic and toxic effects of drugs owing to the major role it plays in xenobiotic metabolism and the large intra- and inter-individual variability to which it is subjected. The functional examination of up to 13 kb of the CYP3A4 5'-flanking region has revealed that the regulation of this gene is a complex issue, with…

The carbon monoxide-releasing molecule CORM-2 inhibits the inflammatory response induced by cytokines in Caco-2 cells

2007

Background and purpose: Recent evidence indicates that carbon monoxide-releasing molecules (CO-RMs) exhibit potential anti-inflammatory properties. In the present study, we have investigated whether tricarbonyl dichloro ruthenium(II) dimer (CORM-2) can control the inflammatory response induced by cytokines in a human colonic epithelial cell line, Caco-2. Experimental approach: Caco-2 cells were preincubated with CORM-2 for 30 minutes and then stimulated with interleukin (IL)-1β, tumor necrosis factor-α and interferon-γ for different times. Gene expression was analyzed by real-time PCR. Protein expression was investigated by Western blot and ELISA. Transcription factor activation was determi…

Mangifera indica L. Extract and Mangiferin Modulate Cytochrome P450 and UDP-Glucuronosyltransferase Enzymes in Primary Cultures of Human Hepatocytes

2012

The aqueous stem bark extract of Mangifera indica L. (MSBE) has been reported to have antioxidant, anti-inflammatory and analgesic properties. In previous studies, we showed that MSBE and mangiferin, its main component, lower the activity of some cytochrome P-450 (P450) enzymes in rat hepatocytes and human liver microsomes. In the present study, the effects of MSBE and mangiferin on several P450 enzymes and UDP-glucuronosyltransferases (UGTs) in human-cultured hepatocytes have been examined. After hepatocytes underwent a 48-h treatment with sub-cytotoxic concentrations of the products (50-250 µg/mL), a concentration-dependent decrease of the activity of the five P450 enzymes measured (CYP1A…

Number and functionality of beta-adrenergic receptors in the mouse lymphocytic P388 leukemia as a doxorubicin-sensitive and -resistant variant.

1992

Symmetry Breaking and Establishment of Dorsal/Ventral Polarity in the Early Sea Urchin Embryo

2015

The mechanisms imposing the Dorsal/Ventral (DV) polarity of the early sea urchin embryo consist of a combination of inherited maternal information and inductive interactions among blastomeres. Old and recent studies suggest that a key molecular landmark of DV polarization is the expression of nodal on the future ventral side, in apparent contrast with other metazoan embryos, where nodal is expressed dorsally. A subtle maternally-inherited redox anisotropy, plus some maternal factors such as SoxB1, Univin, and p38-MAPK have been identified as inputs driving the spatially asymmetric transcription of nodal. However, all the mentioned factors are broadly distributed in the embryo as early as no…

A novel arousal-based individual screening reveals susceptibility and resilience to PTSD-like phenotypes in mice

2021

Translational animal models for studying post-traumatic stress disorder (PTSD) are valuable for elucidating the poorly understood neurobiology of this neuropsychiatric disorder. These models should encompass crucial features, including persistence of PTSD-like phenotypes triggered after exposure to a single traumatic event, trauma susceptibility/resilience and predictive validity. Here we propose a novel arousal-based individual screening (AIS) model that recapitulates all these features. The AIS model was designed by coupling the traumatization (24 h restraint) of C57BL/6 J mice with a novel individual screening. This screening consists of z-normalization of post-trauma changes in startle …

Deploying Genome Editing Tools for Dissecting the Biology of Nut Trees

2019

Walnuts are among the most important nut crops grown in temperate regions of the world. Commercial production in California, and increasingly worldwide, relies on only few clonally grafted scion genotypes, particularly “Chandler,” and more recently clonally propagated disease-resistant rootstocks. Diseases, nematodes, insect pests, abiotic stresses, and other nutritional and environmental factors, can reduce walnut productivity and quality, affecting grower profitability. The California Walnut Breeding Program at UC Davis has developed and released scion cultivars and rootstocks to help address some of these problems. Sequencing of the walnut genome is expected to speed walnut breeding by f…