(C) 2008 Elsevier Inc. All rights reserved.”
“Manipulation of the

ubiquitin proteasome system (UPS) is emerging as a common theme in viral pathogenesis. Some viruses have been shown to encode functional homologs of UPS enzymes, suggesting that a systematic identification of these products may provide new insights into virus-host cell interactions. Ubiquitin-specific proteases, collectively known as deubiquitinating enzymes (DUBs), regulate the activity of the UPS by hydrolyzing ubiquitin peptide or isopeptide bonds. The prediction of viral DUBs based on sequence similarity with known enzymes is selleck chemicals hampered by the diversity of viral genomes. In this study sequence alignments, pattern searches, and hidden Markov models were developed for the conserved C- and H- boxes of the known DUB families and used to search

the open reading frames (ORFs) of Epstein-Barr virus (EBV), a large gammaherpesvirus that has been implicated in the pathogenesis of a broad spectrum of human malignancies of lymphoid and epithelial cell origin. The searches identified a limited number of EBV ORFs that contain putative DUB catalytic domains. DUB activity was confirmed by functional assays and mutation analysis for three high scoring candidates, supporting the usefulness of this bioinformatics approach in predicting distant homologues of cellular enzymes.”
“Polybrominated diphenyl ethers (PBDEs) are used in large quantities as flame-retardant additives, especially in electrical appliances and textiles. Because of their structural similarity, PBDEs are thought to have toxicities similar to those of polychlorinated Sonidegib nmr biphenyls (PCBs), which are well-known persistent compounds. Both 2,2′,4,4′-tetrabromodiphenyl ether (PBDE-47) and 2,2′,4,4′,5, 5′-hexachlorobiphenyl (PCB153) can coexist in the environment and human tissues as dominant congeners of PBDEs and PCBs, respectively. To explore the mechanisms OTX015 nmr of the neurotoxic effect of PBDE-47

and the interaction in combination with PCB153, cell viability, lactate dehydrogenase (LDH) leakage, intracellular Ca(2+) concentration ([Ca(2+)](i)), apoptosis and expression levels of death associated protein kinase (DAPK), caspase3, caspase12 and cytochrome c mRNA and proteins were measured in SH-SY5Y cells treated with PBDE-47 (0,1, 5,10 mu mol/L) and/or PCB153 (5 mu mol/L) for 24 h. Compared to controls, the cell viabilities were clearly decreased (P < 0.05), and LDH leakage, [Ca(2+)](i) and apoptosis were significantly increased (P < 0.05). Furthermore, expression levels of DAPK and caspase3 mRNA, caspase12, as well as cytochrome c mRNA and proteins were markedly increased (P < 0.05), while pro-caspase3 proteins were significantly decreased (P < 0.05). A positive correlation between [Ca(2+)](i) and percentage of apoptotic cells (r = 0.86, P < 0.05) and an interaction between PBDE-47 and PCB153 (P < 0.05) were observed.