Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.61 (caspase-8)
 6,833 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

Low levels of the adipocyte-secreted protein adiponectin correlate with albuminuria in both mice and humans, but whether adiponectin has a causative role in modulating renal disease is unknown. Here, we first generated a mouse model that allows induction of caspase-8-mediated apoptosis specifically in podocytes upon injection of a construct-specific agent. These POD-ATTAC mice exhibited significant kidney damage, mimicking aspects of human renal disease, such as foot process effacement, mesangial expansion, and glomerulosclerosis. After the initial induction, both podocytes and filtration function recovered. Next, we crossed POD-ATTAC mice with mice lacking or overexpressing adiponectin. POD-ATTAC mice lacking adiponectin developed irreversible albuminuria and renal failure; conversely, POD-ATTAC mice overexpressing adiponectin recovered more rapidly and exhibited less interstitial fibrosis. In conclusion, these results suggest that adiponectin is a renoprotective protein after podocyte injury. Furthermore, the POD-ATTAC mouse provides a platform for further studies, allowing precise timing of podocyte injury and regeneration.
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PMID:Adiponectin promotes functional recovery after podocyte ablation. 2333 96