Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.14 (ATP synthase)
 7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although digitalis has been used in clinical treatment extensively, the precise mechanism of its toxic actions on cardiovascular system remained unclear, it would be of interest to study the differential proteomic analysis of vascular endothelial cells in response to toxic concentrations of digitalis thus to provide new agents for treatment of digitalis-induced cytotoxicity. We employed human umbilical vein endothelial cells (HUVEC) as our model system. HUVEC were exposed to increasing concentrations (0.1 nM-10 microM) of digoxin at 12-96 h intervals. Cell viability tests revealed that digoxin played dual effects on cell growth. Apoptosis detection confirmed that apoptosis was primarily responsible for digoxin-induced cell death. Proteomics analysis further revealed that the digoxin-induced apoptosis was accompanied by regulated expression of ATP synthase beta chain, cystatin A, electron transfer flavoprotein, heterogeneous nuclear ribonucleoproteins H3, lamin A, profilin-1, proteasome subunit 5, succinyl-CoA ligase beta chain and heat shock protein 60 (HSP60). Deep study on the overexpression of HSP60 confirmed that HSP60 exerted a protective role in digoxin-induced apoptosis through inhibition of caspase-3 activity in HUVEC. These results provided an impetus for further delineation of mechanism of digoxin-induced cytotoxicity and offered new agents that help attenuate its toxicity.
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PMID:Comparative proteomics analysis reveals role of heat shock protein 60 in digoxin-induced toxicity in human endothelial cells. 1869 61

Better characterization of the molecular mechanisms underlying glomerular cell proliferation may improve our understanding of the pathogenesis of glomerulonephritis and yield disease-specific markers. We used two-dimensional gel electrophoresis (2DE) and mass spectrometry (MS) to generate expression profiles of glomerular proteins in the course of anti-Thy-1 nephritis. Glomeruli were isolated from Wistar rats by sieving, and proteins were separated by 2DE. In preliminary studies using normal rats, we identified known glomerular proteins from microfilaments [tropomyosin (Tm)] and intermediate filaments (vimentin and lamin A), proteins involved in assembly (alpha-actinin-4, F-actin capping protein) and membrane cytoskeletal linking (ezrin), as well as several enzymes (protein disulfide isomerase, ATP synthase, and aldehyde dehydrogenase). Comparison of glomerular protein abundance between normal rats and rats in the early phase of anti-Thy-1 nephritis yielded 28 differentially expressed protein spots. MS analysis identified 16 differentially expressed proteins including Tm. Altered Tm abundance in the course of anti-Thy-1 nephritis was confirmed, and specific isoforms were characterized by Western blotting. We demonstrated a complex change in Tm isoform abundance in the course of anti-Thy-1 nephritis. The early mesangiolytic phase of the disease was characterized by decreased abundance of low-molecular-weight isoforms Tm5a/5b and increased abundance of high-molecular-weight isoforms Tm6, Tm1, Tm2, and Tm3. The late proliferative phase of the disease was associated with increased abundance of isoforms Tm5a/5b, Tm6, and Tm1 and decreased abundance of Tm3. Isoforms Tm4 and Tm5 remained unchanged in the course of this model of experimental glomerulonephritis. Characterization of Tm isoform abundance in the course of clinical glomerulonephritis may identify disease-specific markers.
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PMID:Changes in protein profiles during course of experimental glomerulonephritis. 1898 15