The novel inosine analogue, INO-2002, protects against diabetes development in multiple low-dose streptozotocin and non-obese diabetic mouse models of type I diabetes.
Endogenous purines including inosine have been shown to exert immunomodulatory and anti-inflammatory effects in a variety of disease models. The dosage of inosine required for protection is very high because of the rapid metabolism of inosine in vivo. The aim of this study was to determine whether a metabolic-resistant purine ... More
Xanthine oxidase contributes to mechanical ventilation-induced diaphragmatic oxidative stress and contractile dysfunction.
'Respiratory muscle weakness resulting from both diaphragmatic contractile dysfunction and atrophy has been hypothesized to contribute to the weaning difficulties associated with prolonged mechanical ventilation (MV). While it is clear that oxidative injury contributes to MV-induced diaphragmatic weakness, the source(s) of oxidants in the diaphragm during MV remain unknown. These ... More
Voluntary wheel running restores endothelial function in conduit arteries of old mice: direct evidence for reduced oxidative stress, increased superoxide dismutase activity and down-regulation of NADPH oxidase.
'Habitual aerobic exercise is associated with enhanced endothelium-dependent dilatation (EDD) in older humans, possibly by increasing nitric oxide bioavailability and reducing oxidative stress. However, the mechanisms involved are incompletely understood. EDD was measured in young (6-8 months) and old (29-32 months) cage control and voluntary wheel running (VR) B6D2F1 mice. ... More
Oxidizing Effects of Exogenous Stressors in Huntington's Disease Knock-in Striatal Cells--Protective Effect of Cystamine and Creatine.
AuthorsRibeiro M, Silva AC, Rodrigues J, Naia L, Rego AC,
Journal
PubMed ID24008831
'Huntington''s disease (HD) is a polyglutamine-expansion disease associated to degeneration of striatal and cortical neurons. Previously, we showed that oxidative stress occurs in HD knock-in striatal cells, but little is known regarding cell antioxidant response against exogenous stimuli. Therefore, in the present study we analyzed cellular antioxidant profile following hydrogen ... More
Preserved immune functions and controlled leukocyte oxidative stress in naturally long-lived mice: possible role of nuclear factor kappa B.
AuthorsArranz L, Caamaño JH, Lord JM, De la Fuente M,
JournalJ Gerontol A Biol Sci Med Sci
PubMed ID20558495
'In order to verify the survival biomarker role of several immune functions, and to determine the oxidation and inflammation mechanisms underlying variability in the aging process, we have investigated a variety of immune functions and oxidative stress parameters as well as activation of the nuclear factor kappa B (NF kappaB) ... More
Salicylate treatment improves age-associated vascular endothelial dysfunction: potential role of nuclear factor kappaB and forkhead Box O phosphorylation.
'We hypothesized that I kappa B kinase (IKK)-mediated nuclear factor kappa B and forkhead BoxO3a phosphorylation will be associated with age-related endothelial dysfunction. Endothelium-dependent dilation and aortic protein expression/phosphorylation were determined in young and old male B6D2F1 mice and old mice treated with the IKK inhibitor, salicylate. IKK activation was ... More
Regulation of mitochondrial iron import through differential turnover of mitoferrin 1 and mitoferrin 2.
Mitoferrin 1 and mitoferrin 2 are homologous members of the mitochondrial solute carrier family. Mitoferrin 1 is required for mitochondrial iron delivery in developing erythrocytes. Here we show that mitoferrin 1 and mitoferrin 2 contribute to mitochondrial iron delivery in a variety of cells. Reductions in mitoferrin 1 and/or mitoferrin ... More
Xanthine urolithiasis causing bilateral ureteral obstruction in a 10-month-old cat.
AuthorsMestrinho LA, Gonçalves T, Parreira PB, Niza MM, Hamaide AJ,
JournalJ Feline Med Surg
PubMed ID23413269
Xanthine urolithiasis was diagnosed in a 10-month-old intact female domestic shorthair cat presented with acute renal failure due to bilateral ureteral obstruction. Ultrasonography revealed the presence of multiple uroliths in both kidneys and ureters that were not detectable on previous survey radiographs. Medical management failed and ureteral obstruction persisted with ... More
A role for IOP1 in mammalian cytosolic iron-sulfur protein biogenesis.
AuthorsSong D, Lee FS,
JournalJ Biol Chem
PubMed ID18270200
The biogenesis of cytosolic iron-sulfur (Fe-S) proteins in mammalian cells is poorly understood. In Saccharomyces cerevisiae, there is a pathway dedicated to cytosolic Fe-S protein maturation that involves several essential proteins. One of these is Nar1, which intriguingly is homologous to iron-only hydrogenases, ancient enzymes that catalyze the formation of ... More
RNA silencing of mitochondrial m-Nfs1 reduces Fe-S enzyme activity both in mitochondria and cytosol of mammalian cells.
In prokaryotes and yeast, the general mechanism of biogenesis of iron-sulfur (Fe-S) clusters involves activities of several proteins among which IscS and Nfs1p provide, through cysteine desulfuration, elemental sulfide for Fe-S core formation. Although these proteins have been well characterized, the role of their mammalian homolog in Fe-S cluster biogenesis ... More
Increased iron content and RNA oxidative damage in skeletal muscle with aging and disuse atrophy.
AuthorsHofer T, Marzetti E, Xu J, Seo AY, Gulec S, Knutson MD, Leeuwenburgh C, Dupont-Versteegden EE,
JournalExp Gerontol
PubMed ID18395385
Muscle atrophy with aging or disuse is associated with deregulated iron homeostasis and increased oxidative stress likely inflicting damage to nucleic acids. Therefore, we investigated RNA and DNA oxidation, and iron homeostasis in gastrocnemius muscles. Disuse atrophy was induced in 6- and 32-month old male Fischer 344/Brown Norway rats by ... More
L-Carnitine L-tartrate supplementation favorably affects markers of recovery from exercise stress.
We examined the influence of L-carnitine L-tartrate (LCLT) on markers of purine catabolism, free radical formation, and muscle tissue disruption after squat exercise. With the use of a balanced, crossover design (1 wk washout), 10 resistance-trained men consumed a placebo or LCLT supplement (2 g L-carnitine/day) for 3 wk before ... More
Xanthine oxidase and activated neutrophils cause oxidative damage to skeletal muscle after contractile claudication.
AuthorsJudge AR, Dodd SL
JournalAm J Physiol Heart Circ Physiol
PubMed ID12969896
We previously showed oxidative damage and edema within skeletal muscle after contractile claudication. To investigate the sources of this oxidative damage in the gastrocnemius muscle, we administered allopurinol (Allo, to inhibit xanthine oxidase) and cyclophosphamide (Cyclo, to deplete neutrophils) before inducing contractile claudication in male Sprague Dawley rats. Contractile claudication ... More