Cell-impermeant iron chelator desferrioxamine (DFO) can have access to organelles if appended to suitable vectors. Mitochondria are important targets for the treatment of iron overload-related neurodegenerative diseases. Triphenylphosphonium (TPP) is a delocalized lipophilic cation used to ferry molecules to mitochondria. Here we report the synthesis and characterization of the conjugate TPP-DFO as a mitochondrial iron chelator. TPP-DFO maintained both a high affinity for iron and the antioxidant activity when compared to parent DFO. TPP-DFO was less toxic than TPP alone to A2780 cells (IC = 135.60 ± 1.08 and 4.34 ± 1.06 μmol L, respectively) and its native fluorescence was used to assess its mitochondrial localization (Rr = +0.56). These results suggest that TPP-DFO could be an interesting alternative for the treatment of mitochondrial iron overload e.g. in Friedreich's ataxia.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s10534-017-0039-5 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Interaction and regulation of the mitochondrial proteome - in health and disease.
Expert Rev Proteomics
January 2025
Research Unit for Molecular Medicine, Department of Clinical Medicine, Faculty of Health, Aarhus University, Denmark.
Introduction: Mitochondria contain multiple pathways including energy metabolism and several signaling and synthetic pathways. Mitochondrial proteomics is highly valuable for studying diseases including inherited metabolic disorders, complex and common disorders like neurodegeneration, diabetes and cancer, since they all to some degree have mitochondrial underpinnings.
Areas Covered: The main mitochondrial functions and pathways are outlined and systematic protein lists are presented.
This study primarily investigated the mechanism of Astragalus polysaccharides(APS), a Chinese medicinal material, in regulating the Nrf2/SLC7A11/GPX4 signaling pathway to induce ferroptosis in ovarian cancer cells(Caov-3 and SKOV3 cells). Caov-3 and SKOV3 cells were divided into control(Vehicle) group, APS group, glutathione peroxidase 4 inhibitor(RSL3) group, and APS+RSL3 group. After 48 h of intervention, the activity and morphology of the cells in each group were observed.
View Article and Find Full Text PDFIdentifying disulfidptosis-related biomarkers in epilepsy based on integrated bioinformatics and experimental analyses.
Neurobiol Dis
January 2025
Department of Neurology, the First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, Guangxi, China. Electronic address:
One of the underlying mechanisms of epilepsy (EP), a brain disease characterized by recurrent seizures, is considered to be cell death. Disulfidptosis, a proposed novel cell death mechanism, is thought to play a part in the pathogenesis of epilepsy, but the exact role is unclear. The gene expression omnibus series (GSE) 33,000 and GSE63808 datasets were used to search for differentially expressed disulfidptosis-related molecules (DE-DRMs).
View Article and Find Full Text PDFPeripheral blood immune cells from individuals with Parkinson's disease or inflammatory bowel disease share deficits in iron storage and transport that are modulated by non-steroidal anti-inflammatory drugs.
Neurobiol Dis
January 2025
Center for Translational Research in Neurodegenerative Disease, College of Medicine, University of Florida, Gainesville, FL, USA; Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL, USA; McKnight Brain Institute, University of Florida, Gainesville, FL, USA; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, USA; Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL, USA. Electronic address:
Parkinson's Disease (PD) is a multisystem disorder in which dysregulated neuroimmune crosstalk and inflammatory relay via the gut-blood-brain axis have been implicated in PD pathogenesis. Although alterations in circulating inflammatory cytokines and reactive oxygen species (ROS) have been associated with PD, no biomarkers have been identified that predict clinical progression or disease outcome. Gastrointestinal (GI) dysfunction, which involves perturbation of the underlying immune system, is an early and often-overlooked symptom that affects up to 80 % of individuals living with PD.
View Article and Find Full Text PDF18beta-glycyrrhetinic acid alleviates deoxynivalenol-induced hepatotoxicity by inhibiting GPX4-dependent ferroptosis.
Toxicon
January 2025
School of Basic Medical Sciences, Xianning Medical College, Hubei University of Science and Technology, Xianning, 437100, China; Hubei Key Laboratory of Diabetes and Angiopathy, Medicine Research Institute, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China. Electronic address:
Deoxynivalenol (DON), a mycotoxin that severely contaminates agri-food products can cause hepatotoxicity. Ferroptosis is an iron-dependent form of cell death, and the liver is an important organ for iron accumulation. 18beta-glycyrrhetinic acid (GA) has anti-ferroptosis and hepatoprotective effects.
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!