Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.25.1 (proteasome)
 28,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The proteasome is involved in multiple cellular processes including control of the cell cycle, apoptosis and intracellular signalling; loss of proteasome function has been postulated to participate in the pathogenesis of triplet repeat diseases. We examined the vulnerability of central neurons to proteasome inhibition and tested the ability of anti-excitotoxic and anti-apoptotic treatments to attenuate proteasome inhibition-induced neuronal death. Exposure of murine neocortical cultures to proteasome inhibitors (0.1-10 microm clasto-lactacystin beta-lactone or MG-132) for 48 h resulted in widespread neuronal death associated with a reduction in intracellular free calcium; higher inhibitor concentrations killed astrocytes. Cultured striatal neurons were more vulnerable than cortical neurons. Within each population, the NADPH diaphorase-positive neuronal subpopulation was more vulnerable than the general neuronal population. Enhancing calcium entry with S(-)BayK8644 or kainate, or blocking apoptosis with cycloheximide, actinomycin D or Z-VAD.FMK attenuated neuronal death, whereas, reducing calcium entry with NMDA antagonists or R(+)BayK8644 potentiated neuronal death. These findings suggest that proteasome inhibition can induce selective neuronal apoptosis associated with intracellular calcium starvation, and point to manipulation of intracellular calcium as a specific therapeutic strategy. In particular, concern is raised that glutamate receptor antagonists might exacerbate, rather than attenuate, proteasome inhibition-induced neuronal death.
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PMID:NMDA antagonists exacerbate neuronal death caused by proteasome inhibition in cultured cortical and striatal neurons. 1187 69

The saliva of ticks contains anti-haemostatic, anti-inflammatory and immunomodulatory molecules that allow these parasites to obtain a blood meal from the host and help tick-borne pathogens to infect the vertebrate host more efficiently. This makes the salivary molecules attractive targets to control ticks and tick-borne pathogens. Although Ornithodoros moubata and O. erraticus are important argasid ticks that transmit severe diseases, to date only a few of their salivary proteins have been identified. Here we report our initial studies using proteomic approaches to characterize the protein profiles of salivary gland extracts (SGE) from these two argasids. The present work describes the proteome of the SGEs of both tick species, their antigenic spots, and the identification of several of their proteins. The whole number of identifications was low despite the good general quality of the peptide mass maps obtained. In the O. moubata SGE, 18 isoforms of a protein similar to O. savignyi TSGP1 were identified. In the O. erraticus SGE we identified 6 novel proteins similar to unknown secreted protein DS-1 precursor, NADPH dehydrogenase subunit 5, proteasome alpha subunit, ATP synthase F0 subunit 6, lipocalin and alpha tubulin. Finally, the current drawbacks of proteomics when applied to the identification of acarine peptides and proteins are discussed.
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PMID:A proteomic approach to the identification of salivary proteins from the argasid ticks Ornithodoros moubata and Ornithodoros erraticus. 1791 1

Phthalates are a class of plasticizers that have been characterized as endocrine disrupters, and are associated with genital diseases, cardiotoxicity, hepatotoxicity, and nephrotoxicity in the GeneOntology gene/protein database. In this study, we synthesized phthalic acid chemical probes and demonstrated differing protein-protein interactions between MCF-7 cells and MDA-MB-231 breast cancer cell lines. Phthalic acid chemical probes were synthesized using silicon dioxide particle carriers, which were modified using the silanized linker 3-aminopropyl triethoxyslane (APTES). Incubation with cell lysates from breast cancer cell lines revealed interactions between phthalic acid and cellular proteins in MCF-7 and MDA-MB-231 cells. Subsequent proteomics analyses indicated 22 phthalic acid-binding proteins in both cell types, including heat shock cognate 71-kDa protein, ATP synthase subunit beta, and heat shock protein HSP 90-beta. In addition, 21 MCF-7-specific and 32 MDA-MB-231 specific phthalic acid-binding proteins were identified, including related proteasome proteins, heat shock 70-kDa protein, and NADPH dehydrogenase and ribosomal correlated proteins, ras-related proteins, and members of the heat shock protein family, respectively.
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PMID:Analysis of protein-protein interactions in MCF-7 and MDA-MB-231 cell lines using phthalic acid chemical probes. 2540 41