Geographic characterization of RPE structure and lipid changes in the PEX1-p.Gly844Asp mouse model for Zellweger spectrum disorder DOI Creative Commons
Samy Omri, Catherine Argyriou, Rachel S. Pryce

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 10, 2024

Abstract Peroxisome Biogenesis Disorders-Zellweger Spectrum (PBD-ZSD) are a heterogenous group of autosomal recessive disorders caused by defects in PEX genes whose proteins required for peroxisome assembly and function. Peroxisomes ubiquitous organelles that play critical role complex lipid metabolism. Dysfunctional peroxisomes ZSD cause multisystem effects, with progressive retinal degeneration (RD) leading to childhood blindness being one the most frequent clinical findings. Despite progress understanding normal cellular functions, much remains unknown about how their deficiency causes RD, there is no treatment. To study RD pathophysiology this disease, we used knock-in PEX1-p.GlyG844Asp (G844D) mouse model milder ZSD, which represents common human PEX1-p.Gly843Asp allele. We previously reported diminished function, functional vision, neural retina structural model. Beyond retina, pigment epithelium (RPE) have been patients murine models single enzyme deficiency, suggesting RPE may contribute overall progression disease. Here, investigate phenotype our PEX1-G844D model, observing morphological, inflammatory, changes at 1, 3, 6 months age. report cell appears 3 age worsens time, starts dorsal pole, accompanied subretinal inflammatory infiltration. match these events remodelling using imaging mass spectrometry allowed regional analysis specific layer. identified 47 alterations precede changes, 10 localized pole. 32 persist months, signature 14 new occur concurrent histological changes. Changes peroxisome-dependent lipids detected liquid chromatography tandem (reduced docosahexanoic acid increased very long chain lysophosphatidylcholines) exacerbated over time. This first characterization any animal situ peroxisome-deficient tissue. Our findings reveal candidate drivers could be targeted alleviate as well biomarkers evaluate retinopathy response therapy.

Language: Английский

Facile preparation of Fe3O4/CNTs nanocomposites by catalytic chemical vapor deposition for nonenzymatic hydrogen peroxide sensor DOI
Tian Zhang, Sasa Gu, Wenjie Zhang

et al.

Journal of Alloys and Compounds, Journal Year: 2025, Volume and Issue: unknown, P. 179075 - 179075

Published: Feb. 1, 2025

Language: Английский

Citations

0
Molecular identification of a thioredoxin peroxidase in Babesia gibsoni with potential against oxidative stress DOI Creative Commons
Jiaying Guo, Fangjie Li,

Lingna Wang

et al.

Parasitology Research, Journal Year: 2025, Volume and Issue: 124(3)

Published: March 1, 2025

Language: Английский

Citations

0
Modelling Peroxisomal Disorders in Zebrafish DOI Creative Commons
C. Jiang, Michael Schrader

Cells, Journal Year: 2025, Volume and Issue: 14(2), P. 147 - 147

Published: Jan. 20, 2025

Peroxisomes are ubiquitous, dynamic, oxidative organelles with key functions in cellular lipid metabolism and redox homeostasis. They have been linked to healthy ageing, neurodegeneration, cancer, the combat of pathogens viruses, infection immune responses. Their biogenesis relies on several peroxins (encoded by PEX genes), which mediate matrix protein import, membrane assembly, peroxisome multiplication. Defects or peroxisomal enzymes can result severe disorders, including developmental neurological abnormalities. The drive understand role peroxisomes human health disease, as well their tissues organs during development, has led establishment vertebrate models. zebrafish (Danio rerio) become an attractive model organism investigate functions. Here, we provide overview visualisation zebrafish, metabolic inventory comparison peroxisomes. We then present models established disorders. These include for disorders/Zellweger Spectrum single enzyme deficiencies, particularly adrenoleukodystrophy fatty acid beta-oxidation Finally, highlight deficiencies dually targeted peroxisomal/mitochondrial proteins. Advantages investigation development approaches application drug screening discussed.

Language: Английский

Citations

0
Spatial characterization of RPE structure and lipids in the PEX1-p.Gly844Asp mouse model for Zellweger spectrum disorder DOI Creative Commons
Samy Omri, Catherine Argyriou, Rachel S. Pryce

et al.

Journal of Lipid Research, Journal Year: 2025, Volume and Issue: unknown, P. 100771 - 100771

Published: March 1, 2025

Zellweger Spectrum Disorder (ZSD) is caused by defects in PEX genes, whose proteins are required for peroxisome assembly and function. Peroxisome dysfunction ZSD causes multisystem effects, with progressive retinal degeneration (RD) among the most frequent clinical findings. However, much remains unknown about how deficiency RD. To study RD pathophysiology ZSD, we used PEX1-p.Gly844Asp (G844D) mouse model, which represents common human PEX1-p.Gly843Asp allele. We previously reported diminished function, functional vision, neural retina structural this model. Here, investigate pigment epithelium (RPE) phenotype, examining morphological, inflammatory, lipid changes at 1, 3, 6 months of age. report that RPE cells exhibit evident 3 worsens time, starts dorsal pole, accompanied subretinal inflammatory cell infiltration. match these events imaging mass spectrometry regional analysis lipids RPE. identified 47 alterations preceding changes, 9 localize to pole. 29 persist months, remodeling pole signature. 13 new occur concurrent histological changes. Abnormalities peroxisome-dependent detected LC/MS/MS exacerbated over time. This first characterization a situ peroxisome-deficient tissue. Our findings uncover potential drivers progression identify candidate biomarkers retinopathy response therapy.

Language: Английский

Citations

0
A Simple Methoxyquinoline‐Based Ratiometric Fluorescent Probe for Specific Detection of Hydrogen Peroxide in Living Cells and Zebrafish DOI Open Access

Xinyu Cai,

Xinke Li,

Wenzhai Li

et al.

Luminescence, Journal Year: 2025, Volume and Issue: 40(3)

Published: March 1, 2025

A simple methoxyquinoline-based ratiometric fluorescent probe was synthesized for detecting hydrogen peroxide (H2O2). After the reacted with H2O2, 6-methoxyquinoline fluorescence dye released, and intensity increased at 366 nm decreased 450 nm. And ratio of is linearly related to concentration H2O2 in range 0-100 μM; it shows a good signal. In addition, has characteristics such as rapid response speed high sensitivity selectivity. This low biotoxicity excellent cell membrane permeability further used image HeLa cells zebrafish.

Language: Английский

Citations

0
Analytical subcellular fractionation of microglial BV-2 cells with peroxisomal beta-oxidation defect DOI
Mounia Tahri-Joutey,

Isabelle Hamer,

Virginie Tevel

et al.

Histochemistry and Cell Biology, Journal Year: 2025, Volume and Issue: 163(1)

Published: April 14, 2025

Language: Английский

Citations

0
ROS-mediated regulation of β2AR function: Does oxidation play a meaningful role towards β2-agonist tachyphylaxis in airway obstructive diseases? DOI

Razan L. Teyani,

F. Aarabi Moghaddam,

Nader H. Moniri

et al.

Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: 226, P. 116403 - 116403

Published: June 28, 2024

Language: Английский

Citations

2
SFRRI Inaugural Alberto Boveris Award Lecture Dynamics of Intracellular and Intercellular Redox Communication DOI Creative Commons
Helmut Sies

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 225, P. 933 - 939

Published: Nov. 1, 2024

Language: Английский

Citations

2
Dual Gold Nanostructures-Based Stretchable Electrochemiluminescence Sensors for Hydrogen Peroxide Monitoring in Endothelial Mechanotransduction DOI
Hao Liu, Qian Wang, Shibo Cheng

et al.

ACS Sensors, Journal Year: 2024, Volume and Issue: 9(11), P. 6276 - 6283

Published: Nov. 7, 2024

Hydrogen peroxide (H

Language: Английский

Citations

2
Research progress in mechanism of anticancer action of shikonin targeting reactive oxygen species DOI Creative Commons

Qi Ke,

Jiayi Li, Yang Hu

et al.

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

Published: July 11, 2024

Excessive buildup of highly reactive molecules can occur due to the generation and dysregulation oxygen species (ROS) their associated signaling pathways. ROS have a dual function in cancer development, either leading DNA mutations that promote growth dissemination cells, or triggering death cells. Cancer cells strategically balance fate by modulating levels, activating pro-cancer pathways, suppressing antioxidant defenses. Consequently, targeting has emerged as promising strategy therapy. Shikonin its derivatives, along with related drug carriers, impact several pathways components involved oxidative stress induce processes such apoptosis, necroptosis, cell cycle arrest, autophagy, well modulation ferroptosis. Moreover, they increase responsiveness drug-resistant chemotherapy drugs, based on specific characteristics ROS, kind stage cancer. This research explores anti-cancer impacts summarize mechanisms achievements shikonin-targeted effects provide suggestions for designing further anti-tumor experiments undertaking experimental practical research.

Language: Английский

Citations

1