Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proteome analysis of human umbilical endothelial cells was performed to identify proteins that are modified during vascular endothelial cell growth factor (VEGF)-induced transition from the quiescent into the proliferating-migrative phenotype. Subtractive analysis of two-dimensional gel patterns of human endothelial cells, before and after stimulation with VEGF(165), revealed differences in 85 protein spots. All proteins were identified by peptide sequencing and peptide mass fingerprinting using an electrospray spectrometer. The proteins identified were members of specific families including Ca(2+)-binding proteins, fatty-acid binding proteins, structural proteins, and chaperones. Remarkably, there was a massive activation of cellular machinery for both protein synthesis and protein degradation. Thus, among up-regulated proteins there were members of all groups of heat shock proteins (HSPs; HSP 27, HSP 60, HSP 70p5, HSP 70p8, HSP 90, and HSP 96) and some other proteins showing either chaperone activity or which participate in assembly of multimolecular structures (TCP-1, desmoplakins, junction plakoglobin, GRP 94, thioredoxin related protein, and peptidylprolyl isomerase). The increased expression of HSPs was confirmed at the mRNA level at different stages of treatment with VEGF. Similarly, components of the proteolytic machinery for the degradation of misfolded proteins (ER-60, cathepsin D, proteasome subunits, and protease inhibitor 6) were also up-regulated. On the other hand, changes in the expression of structural proteins (T-plastin, vimentin, alpha tubulin, actin, and myosin) could account, at least in part, for the different morphologies displayed by migrating endothelial cells. In summary, our data show that VEGF levels similar to those during physiological stresses induce a number of genes and multiple endogenous pathways seem to be engaged in restoring cellular homeostasis. To ensure cell survival, the molecular chaperones (the heat shock family of stress proteins) are highly up-regulated providing protein-folding machinery to repair or degrade misfolded proteins.
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PMID:Heat shock proteins and other components of cellular machinery for protein synthesis are up-regulated in vascular endothelial cell growth factor-activated human endothelial cells. 1576 53

Using a proteomic approach, we characterized different protein expression profiles in anterior gills of the Chinese mitten crab, Eriocheir sinensis, after cadmium (Cd) exposure. Two experimental conditions were tested: (i) an acute exposure (i.e. 500 microg Cd l(-1) for 3 days) for which physiological, biochemical and ultrastructural damage have been observed previously; (ii) a chronic exposure (i.e. 50 microg Cd l(-1) for 30 days) resulting in physiological acclimation, i.e. increased resistance to a subsequent acute exposure. Two-dimensional gel electrophoresis (2-DE) revealed six protein spots differentially expressed after acute, and 31 after chronic Cd exposure. From these spots, 15 protein species were identified using MS/MS micro-sequencing and MS BLAST database searches. Alpha tubulin, glutathione S-transferase and crustacean calcium-binding protein 23 were down-regulated after an acute exposure, whereas another glutathione S-transferase isoform was up-regulated. Furthermore, analyses revealed the over-expression of protein disulfide isomerase, thioredoxin peroxidase, glutathione S-transferase, a proteasome subunit and cathepsin D after chronic exposure. Under the same condition, ATP synthase beta, alpha tubulin, arginine kinase, glyceraldehyde-3-phosphate dehydrogenase and malate dehydrogenase were down-regulated. These results demonstrate that acute and chronic exposure to waterborne Cd induced different responses at the protein expression level. Protein identification supports the idea that Cd mainly exerts its toxicity through oxidative stress induction and sulfhydryl-group binding. As a result, analyses showed the up-regulation of several antioxidant enzymes and chaperonins during acclimation process. The gill proteolytic capacity seems also to be increased. On the other hand, the clearly decreased abundance of several enzymes involved in energy transfer suggests that chronic metal exposure induced an important metabolic reshuffling.
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PMID:Differential protein expression profiles in anterior gills of Eriocheir sinensis during acclimation to cadmium. 1624 38