Positron emission tomography probe demonstrates a striking concentration of ribose salvage in the liver.

Proc Natl Acad Sci U S A

Departments of Microbiology, Immunology, and Molecular Genetics,Molecular and Medical Pharmacology,Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, andHoward Hughes Medical Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095

Published: July 2014

PET is a powerful technique for quantifying and visualizing biochemical pathways in vivo. Here, we develop and validate a novel PET probe, [(18)F]-2-deoxy-2-fluoroarabinose ([(18)F]DFA), for in vivo imaging of ribose salvage. DFA mimics ribose in vivo and accumulates in cells following phosphorylation by ribokinase and further metabolism by transketolase. We use [(18)F]DFA to show that ribose preferentially accumulates in the liver, suggesting a striking tissue specificity for ribose metabolism. We demonstrate that solute carrier family 2, member 2 (also known as GLUT2), a glucose transporter expressed in the liver, is one ribose transporter, but we do not know if others exist. [(18)F]DFA accumulation is attenuated in several mouse models of metabolic syndrome, suggesting an association between ribose salvage and glucose and lipid metabolism. These results describe a tool for studying ribose salvage and suggest that plasma ribose is preferentially metabolized in the liver.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4104878PMC
http://dx.doi.org/10.1073/pnas.1410326111DOI Listing

Publication Analysis

Top Keywords

ribose salvage
16
ribose
9
ribose preferentially
8
positron emission
4
emission tomography
4
tomography probe
4
probe demonstrates
4
demonstrates striking
4
striking concentration
4
concentration ribose
4

Similar Publications

Tacrolimus (TAC)-induced chronic nephrotoxicity (TAC nephrotoxicity) is a serious issue for long-term graft survival in kidney transplantation. However, the pathophysiology of TAC nephrotoxicity remains unclear. In this study, we analyzed whole blood samples from mice that developed TAC nephrotoxicity in order to discover its mechanism.

View Article and Find Full Text PDF

Niraparib perturbs autophagosome-lysosome fusion in pancreatic ductal adenocarcinoma and exhibits anticancer potential against gemcitabine-resistant PDAC.

Transl Oncol

January 2025

State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China. Electronic address:

While poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi) have achieved specific clinical benefits in a subset of pancreatic ductal adenocarcinoma (PDAC) patients, the potential role of the PARPi niraparib in PDAC necessitates further exploration. In this study, we demonstrated that Niraparib exhibited a pronounced inhibitory effect on autophagy in PDAC both in vitro and in vivo. Mechanistically, this inhibition was primarily attributed to niraparib's ability to disrupt the fusion process between autophagosomes and lysosomes, while potentially exerting a relatively minor impact on the initial stage of autophagy.

View Article and Find Full Text PDF

Purpose Of This Document: The Oncology Committee of the French Urology Association is proposing updated recommendations for the management of recurrent and/or metastatic prostate cancer (PCa).

Methods: A systematic review of the literature from 2022 to 2024 was conducted by the CCAFU on the therapeutic management of recurrent PCa following local or metastatic treatment, assessing the references based on their level of evidence.

Results: Molecular imaging is the standard approach for assessing recurrence after local treatment and should not delay early salvage treatment.

View Article and Find Full Text PDF

Ablation of NAMPT in dopaminergic neurons leads to neurodegeneration and induces Parkinson's disease in mouse.

Brain Res Bull

November 2024

Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China; Zhejiang Province Key Laboratory of Mental Disorder's Management, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China. Electronic address:

Article Synopsis
  • - Nicotinamide phosphoribosyltransferase (NAMPT) is vital for producing nicotinamide adenine dinucleotide (NAD) and has been studied for its protective effects in neurodegeneration, particularly in Alzheimer's Disease, but its role in Parkinson's Disease (PD) is less understood.
  • - Research indicates that dopaminergic neurons in the substantia nigra have higher NAMPT levels, and removing NAMPT leads to the loss of these neurons, dopamine pathway impairment, and symptoms similar to PD in mice.
  • - The study suggests that NAD precursor nicotinamide ribose (NR) can counteract neurodegeneration in PD by repairing dopamine pathways and highlights the potential for using NAD precursors in
View Article and Find Full Text PDF

Engineering a Bifunctional Fusion Purine/Pyrimidine Nucleoside Phosphorylase for the Production of Nucleoside Analogs.

Biomolecules

September 2024

Applied Biotechnology Group, Universidad Europea de Madrid, Urbanización El Bosque, Villaviciosa de Odón, 28670 Madrid, Spain.

Article Synopsis
  • * The study introduces engineered bifunctional fusion enzymes from purine nucleoside phosphorylase I (PNP I) and thymidine phosphorylase (TP), offering a more efficient one-pot synthesis method for nucleosides, as opposed to traditional multi-enzyme systems.
  • * These fusion enzymes operate well at high temperatures (60-90 °C) and specific pH levels (6-8), demonstrating strong stability and successful catalysis for various nucleoside analogs, highlighting their potential in
View Article and Find Full Text PDF

Want 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!