Cytochrome P450 (CYP) enzymes are key players in drug metabolism. Therefore, it is essential to understand how these enzymes can be affected by xenobiotics with regards to induction and toxicity to avoid potential drug-drug interactions. Typically, information has been gathered by combining data from multiple experiments, which is time-consuming and labor intensive, and interassay variability may lead to misinterpretation. Monitoring CYP induction and cytotoxicity by xenobiotics using an automated, multiplexed format can decrease workload and increase data confidence. Here the authors demonstrate the ability to monitor CYP1A and CYP3A4 induction, combined with a cytotoxicity measurement, from a single microplate well using cryopreserved human hepatocytes. The assay procedure was automated in a 384-well format, including cell manipulations, compound titration and transfer, and reagent dispensing, using simple robotic instrumentation. EC(50) and E(max) values were derived for multiple known CYP1A and -3A4 inducers. Induction and toxicological responses in the triplex system were validated based on literature values from conventional single-parameter assays. Validation and pharmacology data confirm that multiplexed cell-based CYP assays can simplify workload, save time and effort, and generate biologically relevant data.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1177/1087057111411482 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Metabolic adaptations to acute glucose uptake inhibition converge upon mitochondrial respiration for leukemia cell survival.
Cell Commun Signal
January 2025
Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.
One hallmark of cancer is the upregulation and dependency on glucose metabolism to fuel macromolecule biosynthesis and rapid proliferation. Despite significant pre-clinical effort to exploit this pathway, additional mechanistic insights are necessary to prioritize the diversity of metabolic adaptations upon acute loss of glucose metabolism. Here, we investigated a potent small molecule inhibitor to Class I glucose transporters, KL-11743, using glycolytic leukemia cell lines and patient-based model systems.
View Article and Find Full Text PDFLight and dark biofilm adaptation impacts larval settlement in diverse coral species.
Environ Microbiome
January 2025
Australian Centre for Ecogenomics, School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia.
Background: Recovery of degraded coral reefs is reliant upon the recruitment of coral larvae, yet the mechanisms behind coral larval settlement are not well understood, especially for non-acroporid species. Biofilms associated with reef substrates, such as coral rubble or crustose coralline algae, can induce coral larval settlement; however, the specific biochemical cues and the microorganisms that produce them remain largely unknown. Here, we assessed larval settlement responses in five non-acroporid broadcast-spawning coral species in the families Merulinidae, Lobophyllidae and Poritidae to biofilms developed in aquaria for either one or two months under light and dark treatments.
View Article and Find Full Text PDFOocytes with impaired meiotic maturation contain increased mtDNA deletions.
J Assist Reprod Genet
January 2025
UMass Memorial Medical Center, Memorial Campus, 119 Belmont St, Worcester, MA, 01605, USA.
Purpose: Induction of meiotic competence is a major goal of the controlled ovarian stimulation used in ART. Do factors intrinsic to the oocyte contribute to oocyte maturation? Deletions in mtDNA accumulate in long-lived post mitotic tissues and are found in human oocytes. If oogenesis cleanses the germline of deleterious deletions in mtDNA, meiotically competent oocytes should contain lower levels of mtDNA deletions vs.
View Article and Find Full Text PDFDevelopment and characterization of in vitro inducible immortalization of a murine microglia cell line for high throughput studies.
Sci Rep
January 2025
Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, United States.
There are few in vitro models available to study microglial physiology in a homeostatic context. Recent approaches include the human induced pluripotent stem cell model, but these can be challenging for large-scale assays and may lead to batch variability. To advance our understanding of microglial biology while enabling scalability for high-throughput assays, we developed an inducible immortalized murine microglial cell line using a tetracycline expression system.
View Article and Find Full Text PDFControlling the energies of the single-rotor large wind turbine system using a new controller.
Sci Rep
January 2025
Department of Electrical Engineering, College of Engineering, King Khalid University, P.O. Box 394, Abha, 61421, KSA, Saudi Arabia.
In wind energy generation systems, ensuring high energy quality is critical but is often compromised due to the limited performance and durability of conventional regulators. To address this, this work presents a novel controller for managing the machine-side inverter of a single-rotor large wind turbine system using an induction machine-type generator. The proposed controller is designed using proportional, integral, and derivative error-based mechanisms, which fundamentally differ from traditional proportional-integral (PI) regulators.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!