Practical Aspects of Flavin-Containing Monooxygenase-Mediated Metabolism DOI
John R. Cashman

Chemical Research in Toxicology, Journal Year: 2024, Volume and Issue: 37(11), P. 1776 - 1793

Published: Nov. 1, 2024

Hepatic flavin-containing monooxygenase 3 (FMO3) is arguably the most important FMO in humans from standpoint of drug metabolism. Recently, adult hepatic FMO3 has been linked to several conditions including cardiometabolic diseases, aging, obesity, and atherosclerosis small animals. Despite importance chemical metabolism, relative cytochrome P-450 (CYP), fewer studies have published describing This may be due properties human FMO3. For example, thermally labile, often methods reported study are not optimal. Herein, I describe some practical aspects for studying other FMOs.

Language: Английский

Contribution of cuproptosis and immune-related genes to idiopathic pulmonary fibrosis disease DOI Creative Commons

Chengji Jin,

Jia Li, Qiaoyu Li

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 7, 2025

Idiopathic pulmonary fibrosis (IPF) is a degenerative respiratory condition characterized by significant mortality rates and scarcity of available treatment alternatives. Cuproptosis, novel form copper-induced cell death, has garnered attention for its potential implications. The study aimed to explore the diagnostic value cuproptosis-related hub genes in patients with IPF. Additionally, multiple bioinformatics analyses were employed identify immune-related biomarkers associated diagnosis IPF, offering valuable insights future strategies. Four microarray datasets selected from Gene Expression Omnibus (GEO) collection screening. Differentially expressed (DEGs) IPF analyzed. weighted gene coexpression network analysis (WGCNA) was DEGs most Ultimately, we analyzed five assessed their both training validation sets. four screened using protein-protein interaction (PPI) evaluated through receiver operating characteristic (ROC) curve. Lastly, single-cell RNA-seq further investigate differential distribution. We identified total 92 DEGs. Bioinformatics highlighted as candidate biomarkers, including three upregulated (CFH, STEAP1, HDC) two downregulated (NUDT16 FMO5). accuracy these cohort confirmed be reliable. that demonstrated strong performance CXCL12 showing an AUROC 0.90. also examined relationship between immune cells. significantly negatively neutrophils, while CXCR2 exclusively consistent our sequencing results. CTSG showed primarily positive association follicular helper T, SPP1 strongly macrophages. Finally, data revealed highly endothelial subset (ECs), exhibited high expression cellular populations. statistically differences monocyte research methodically depicted intricate interplay among genes, new ideas diagnosing treating

Language: Английский

Citations

0
Puerarin ameliorates non-alcoholic fatty liver disease by inhibiting lipid metabolism through FMO5 DOI Creative Commons

Zhaoyi Li,

Wenjing Cao, Yuxuan Zhang

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: July 11, 2024

Introduction: Pueraria lobata is traditionally used in China for treatment of non-alcoholic fatty liver disease (NAFLD). Puerarin, a functional drug extracted from , features pharmacological activity. The present study aims to investigate the effect puerarin intervention on NAFLD. Methods: We established an NAFLD mouse model using high-fat diet with 60% fat and evaluated impact intervention. Results discussion: Our results demonstrate that significantly ameliorates lipid accumulation protects high-fat-induced damage while reducing oxidative stress levels liver. Furthermore, downregulates transcription acetyl-CoA carboxylase (ACC1) It also upregulates carnitine palmitoyltransferase 1 (CPT1), peroxisome proliferator-activated receptor alpha (PPARα), proliferators-activated γ coactivator (PGC1α), which are related oxidation. we demonstrated flavin-containing monooxygenase (FMO5) was involved protective against NFALD. In conclusion, beneficial showed could prevent injury caused by via activating FMO5. These findings provide new theoretical basis applying as therapeutic agent

Language: Английский

Citations

3
The Impact of SLC2A8 RNA Interference on Glucose Uptake and the Transcriptome of Human Trophoblast Cells DOI Creative Commons
Aleksandra Lipka, Łukasz Paukszto, Victoria C. Kennedy

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(5), P. 391 - 391

Published: Feb. 24, 2024

While glucose is the primary fuel for fetal growth, placenta utilizes majority of taken up from maternal circulation. Of facilitative transporters in placenta, SLC2A8 (GLUT8) thought to primarily function as an intracellular transporter; however, its trophoblast cells has not been determined. To gain insight into lentiviral-mediated RNA interference (RNAi) was performed human first-trimester cell line ACH-3P. Non-targeting sequence controls (NTS RNAi; n = 4) and RNAi (n infected ACH-3P were compared. A 79% reduction mRNA concentration associated with 11% (p ≤ 0.05) uptake. NTS subjected RNAseq, identifying 1525 transcripts that differentially expressed (|log2FC| > 1 adjusted p-value < 0.05), 273 derived protein-coding genes, change 10 these mRNAs validated by real-time qPCR. Additionally, there 147 long non-coding RNAs. Functional analyses revealed genes involved various metabolic pathways cellular respiration, oxidative phosphorylation, ATP synthesis. Collectively, data indicate deficiency may impact placental uptake glucose, but likely support respiration. Since oxidizes it takes own needs, impairment could set stage functional insufficiency.

Language: Английский

Citations

2
Flavin‐containing monooxygenase (FMO): Beyond xenobiotics DOI
Ajay Bhat,

Faith R. Carranza,

Angela M. Tuckowski

et al.

BioEssays, Journal Year: 2024, Volume and Issue: 46(7)

Published: May 7, 2024

Flavin-containing monooxygenases (FMOs), traditionally known for detoxifying xenobiotics, are now recognized their involvement in endogenous metabolism. We recently discovered that an isoform of FMO, fmo-2 Caenorhabditis elegans, alters metabolism to impact longevity and stress tolerance. Increased expression C. elegans modifies the flux through key pathway as One Carbon Metabolism (OCM). This modified results a decrease ratio S-adenosyl-methionine (SAM) S-adenosyl-homocysteine (SAH), consequently diminishing methylation capacity. Here we discuss how FMO-2-mediated formate production during tryptophan may serve trigger changing OCM. suggest bridges OCM, altering metabolic away from overexpression. Additionally, highlight these intersect with mTOR AMPK pathways, addition mitochondrial In conclusion, goal this essay is bring attention central role FMO enzymes but lack understanding mechanisms. justify call deeper enzyme's rewiring tryptophan/formate or other yet unidentified substrates. emphasize identification novel drugs microbes induce activity extend lifespan.

Language: Английский

Citations

1
Practical Aspects of Flavin-Containing Monooxygenase-Mediated Metabolism DOI
John R. Cashman

Chemical Research in Toxicology, Journal Year: 2024, Volume and Issue: 37(11), P. 1776 - 1793

Published: Nov. 1, 2024

Hepatic flavin-containing monooxygenase 3 (FMO3) is arguably the most important FMO in humans from standpoint of drug metabolism. Recently, adult hepatic FMO3 has been linked to several conditions including cardiometabolic diseases, aging, obesity, and atherosclerosis small animals. Despite importance chemical metabolism, relative cytochrome P-450 (CYP), fewer studies have published describing This may be due properties human FMO3. For example, thermally labile, often methods reported study are not optimal. Herein, I describe some practical aspects for studying other FMOs.

Language: Английский

Citations

0