benzyloxycarbonylleucyl-leucyl-leucine-aldehyde and Uremia

benzyloxycarbonylleucyl-leucyl-leucine-aldehyde has been researched along with Uremia* in 2 studies

Other Studies

2 other study(ies) available for benzyloxycarbonylleucyl-leucyl-leucine-aldehyde and Uremia

ArticleYear
Uraemic serum induces dysfunction of vascular endothelial cells: role of ubiquitin-proteasome pathway.
    Experimental physiology, 2011, Volume: 96, Issue:8

    The ubiquitin-proteasome pathway (UPP) has been indicated to contribute to dysfunction of endothelial cells (ECs). Nevertheless, the relationship between UPP and vascular complications of uraemia remains unknown. We aimed to determine whether the UPP is activated in vascular ECs when cultured with uraemic serum, and to examine the role of the UPP on dysfunction of ECs in uraemia. Rabbit aortic endothelial cells (RAECs) were cultured with normal serum or different concentrations of uraemic serum. The expression of the ubiquitin-activating enzyme (E1), an indicator of the UPP, was detected by real-time RT-PCR and Western blot; proteasome activity was determined by fluorescence spectrophotometry; and nuclear factor-κB (NF-κB) activity and expression, as well as tumour necrosis factor-α (TNF-α) expression, were also detected. We found that the expression of E1 and the activities of three kinds of proteasomes were increased significantly in RAECs after incubation with uraemic serum. Proliferation of RAECs was increased significantly by incubation with 3-15% uraemic serum but decreased markedly when incubated with uraemic serum above 15% (increased apoptosis). Incubation of RAECs with uraemic serum induced increased NF-B DNA-binding activity and nuclear translocation of NF-κB, decreased nitric oxide production and increased expression of TNF-α, which is the final effector of inflammatory activation of cells. All of these responses in RAECs were suppressed by the specific proteasome inhibitor, MG132. The inhibition of inflammatory responses by MG132 was further supported by a parallel experiment with pyrrolidine dithiocarbamate, a specific inhibitor of κNF-B. These findings suggest that the UPP was activated in RAECs by administration of uraemic serum, and played a pivotal role in the dysfunction of vascular ECs, such as inflammatory activation.

    Topics: Animals; Apoptosis; Cell Cycle; Cell Nucleus; Cell Proliferation; Cells, Cultured; DNA-Binding Proteins; Endothelial Cells; Inflammation; Leupeptins; NF-kappa B; Nitric Oxide; Proteasome Endopeptidase Complex; Proteasome Inhibitors; Protein Binding; Protein Transport; Pyrrolidines; Rabbits; Signal Transduction; Thiocarbamates; Tumor Necrosis Factor-alpha; Ubiquitin; Ubiquitin-Activating Enzymes; Uremia

2011
Preventive effect of a proteasome inhibitor on the formation of accelerated atherosclerosis in rabbits with uremia.
    Journal of cardiovascular pharmacology, 2010, Volume: 55, Issue:2

    Inflammation plays a central role in the pathogenesis of atherosclerosis. This study investigated whether the proteasome inhibitor has the same preventive effect on the formation of accelerated atherosclerosis in rabbits with uremia compared with a NF-kappaB inhibitor. New Zealand white rabbits were subjected to five-sixths nephrectomy (chronic renal failure [CRF]) or to a sham operation. Rats in each group were randomly assigned into three subgroups (n = 24 in each group) and treated with repeated intramuscular injections of proteasome inhibitor MG132 or NF-kappaB inhibitor PDTC for a specified period. Compared with sham rabbits, CRF rabbits displayed typical atherosclerotic changes (endothelial cell damage, intimal thickens, and appearance of foam cells). CRF rabbits had significantly higher levels of proteasome activity, NF-kappaB mRNA, protein, and DNA binding activity as well as tumor necrosis factor-a and proliferative cell nuclear antigen protein expression in aortic wall cells. CRF rabbits also showed lower levels of IkappaBalpha. Compared with CRF rabbits, CRF rabbits treatment with proteasome inhibitor MG132 showed restoration of IkappaBalpha mRNA and protein expression and decreased NF-kappaB DNA binding activity and tumor necrosis factor-a expression. Treatment with either proteasome inhibitor MG132 or NF-kappaB inhibitor PDTC could reverse these pathologic changes in the aortic wall cells of CRF rabbits. A comparison between the inhibitory effects of the two treatments revealed no statistical difference. These results suggest that ubiquitin-proteasome activation play a pivotal role in the pathogenesis of uremia-accelerated atherosclerosis. The ubiquitin-proteasome signaling pathway in aortic cells may therefore be an important target for preventing uremia-accelerated atherosclerosis.

    Topics: Animals; Atherosclerosis; Leupeptins; Protease Inhibitors; Proteasome Endopeptidase Complex; Proteasome Inhibitors; Rabbits; Uremia

2010
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