Ferrocene, a stable, synthetic, iron-containing compound induces in vitro and in vivo activation of mouse lymphocytes and macrophages. Ferrocene also has a marked antitumor effect in mice, upon its administration intraperitoneally and in drinking water. Ferrocene's antitumor activity is attributed to its immune-stimulatory property. This conclusion is supported by adoptive transfer experiments demonstrating that immune cells from ferrocene-treated tumor-bearing mice elicit an antitumor effect in mice not treated with ferrocene. We postulate that the immune stimulatory effect of ferrocene is mediated by redox-sensitive signaling such as activation of p21ras. This postulation is supported by the following findings: Ferrocene generates H2O2 by autooxidation; N-acetylcysteine, a free-radical scavenger, reduces its antitumor effect; and it stimulates GTPase activity catalyzed by pure recombinant p21ras and activates ERK 1/2 in wild Jurkat T cells but fails to do so in the Jurkat T cells expressing p21ras in which cysteine 118 was replaced by serine. Lastly, ferrocene activates and translocates NF-kappaB in human PBM, a pathway which is mediated by ras. It is most plausible that additional redox-sensitive signaling proteins mediate the biological effects of ferrocene.
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http://dx.doi.org/10.1096/fj.02-0558fje | DOI Listing |
Antioxid Redox Signal
December 2024
Department of Medicine-Western Health, Melbourne Medical School, The University of Melbourne, Parkville, Australia.
Inflammation and oxidative stress play crucial roles in the development and progression of skeletal muscle diseases. This review aims to examine the existing evidence regarding the involvement and inhibition of APE1/Ref-1 (apurinic/apyrimidinic endonuclease 1/redox factor 1) in diseases, then extrapolate this evidence to the context of skeletal muscle and discuss the potential beneficial effects of APE1/Ref-1 inhibition in ameliorating myopathy with a particular focus on dystrophic pathology. Currently, therapeutic interventions targeting pathways, such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nuclear factor erythroid 2-related factor 2 (NRF2), have shown limited efficacy in both clinical and preclinical settings.
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Department of Plant Biotechnology and Bioinformatics, Ghent University, 9052 Ghent, Belgium.
In aerobic life forms, reactive oxygen species (ROS) are produced by the partial reduction of oxygen during energy-generating metabolic processes. In plants, ROS production increases during periods of both abiotic and biotic stress, severely overloading the antioxidant systems. Hydrogen peroxide (H2O2) plays a central role in cellular redox homeostasis and signaling by oxidising crucial cysteines to sulfenic acid, which is considered a biologically relevant post-translational modification (PTM).
View Article and Find Full Text PDFFree Radic Biol Med
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MRC-Versus Arthritis Centre for Integrated Research Into Musculoskeletal Ageing (CIMA), Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, France. Electronic address:
Skeletal muscle generates superoxide during contractions, which is converted to hydrogen peroxide (HO). HO has been proposed to activate signalling pathways and transcription factors that regulate adaptive responses to exercise, but the concentration required to oxidize and activate key redox-sensitive signalling proteins in vitro is much higher than the typical intracellular levels seen in muscle after exercise. We hypothesized that 2-Cys-peroxiredoxins (PRDX), which rapidly oxidize in the presence of physiological concentrations of HO, serve as intermediary signalling molecules and play a crucial role in activating adaptive pathways following muscle contractions.
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Pharmacology and Toxicology Department, Faculty of Pharmacy, Nile Valley (NVU) University, Fayoum, Egypt.
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View Article and Find Full Text PDFJ Lipid Res
November 2024
Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Health Sciences Mass Spectrometry Core, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address:
The enzymatic oxidation of arachidonic acid is proposed to yield trihydroxytetraene species (termed lipoxins) that resolve inflammation via ligand activation of the formyl peptide receptor, FPR2. While cell and murine models activate signaling responses to synthetic lipoxins, primarily lipoxin A (LXA), there are expanding concerns about the reported biological formation, detection, and signaling mechanisms ascribed to LXA and related di- and tri-hydroxy ω-6 and ω-3 fatty acids. The generation and signaling actions of LXA and its primary 15-oxo metabolite were assessed in control, lipopolysaccharide-activated, and arachidonic acid-supplemented RAW264.
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