Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Uremic patients have a higher risk of infection and malignancy than normal subjects. Previous studies have deomonstrated that monocytes isolated from uremic patients display an increased apoptosis rate compared to normal subjects; furthermore uremic plasma can increase apoptosis rates on U937, a human monocytic cell line. In several pathological conditions, precipitation of uric acid crystals can lead to renal insufficiency or acute renal failure by different mechanisms. In recent studies uric acid has been shown to induce inflammatory response from monocytes and it has been suggested to be involved in cell dysfunction. Rasburicase is a new recombinant urate oxidase developed to prevent and treat hyperuricaemia in patients with cancer or renal failure; it degrades uric acid to allantoin, a less toxic and more soluble product. In the present study, we aimed at determining whether uric acid may be a factor affecting U937 apoptosis, and whether urate oxidase may reduces or even prevent uric acid induced cell apoptosis. Hoechst staining and internucleosome ledder fragmentation of DNA showed that uric acid increased the percentage of apoptotic cells comparing to the control and that when the U937 cells were incubated with uric acid and urate oxidase the percentage of apoptosis significantly decreased (from 43+/-7% to 19+/- 3%, p<0.05). Also, the activity of caspase-8 and caspase-3 showed the same trend (caspase 3: from 2.7+/-0.53 to 1.6+/-0.42; caspase-8: from 2.2+/-0.43 to 1.3+/-0.57). A reduction of intracellular reduced glutathione (GSH) concentration was found in uric acid treated cells while the addition of urate oxidase in the uric acid incubated cells decreased the GSH extrusion. The concentration of TNF-alpha was increased in the sample incubated with uric acid comparing to the control. Uric acid is an inducer of apoptosis on U937 cell line, and therefore it may be a component of the mosaic of uremic toxins both in acute and chronic renal disease. We can hypothesize that uric acid might be directly involved in the apoptotic process trough the activation of both death receptor and mitochondrial-mediated pathways. We have, also, demonstrated that urate oxidase is able to prevent at least in part, the effect of uric acid on U937 apoptosis. This effect might be a result of different mechanisms of action.
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PMID:Protective effect of urate oxidase on uric acid induced-monocyte apoptosis. 1647 39

This research reports on the cytotoxicity of materials present in a wound biosensor on human keratinocytes (HaCaT) to evaluate the biocompatibility of the sensor for continuous wound monitoring applications. Individual and collective effects of the sensor materials, gold (Au) and silver (Ag) nanoparticles (NPs), uricase enzyme (UOx), ferrocene carboxylic acid (FCA), multi-walled carbon nanotubes (MWCNTs) and poly vinyl alcohol-based polymer (PVA-SbQ) on HaCaT were studied. The toxicology profiles of these materials were derived from cell viability, mitochondrial activity retention and apoptotic behavior studies. At the concentrations present in the sensor, the cell viability studies showed minimal toxicity for Au and Ag NPs, UOx and FCA (cell viability >75%), while MWCNTs and PVA-SbQ exhibited excellent biocompatibility towards keratinocytes (cell viability >90%). Resazurin assay confirmed minimal impairment of mitochondrial activity at lower concentrations for all the materials (mitochondrial activity >0.7). The caspase-3/7 apoptotic assay showed no pronounced apoptotic behavior caused by the materials. The material mixtures studied were Au/UOx/FCA/PVA-SbQ, Ag/UOx/FCA/PVA-SbQ, and MWCNTs/UOx/FCA/PVA-SbQ. A higher toxicity profile was observed for the heterogeneous material mixtures as a result of the cumulative effect of the individual materials. However, the biosensor itself was seen to exhibit lower toxicity (~5%) compared to the material mixtures, due to the protective PVA-SbQ capping over the biosensor. This work establishes the biocompatibility of the reported wound sensor for human measurements with minimal toxic effects on human keratinocytes.
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PMID:Toxicity assessment of wearable wound sensor constituents on keratinocytes. 3092 93