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)

The purpose of this study was to investigate the effect of the nonglucocorticoid steroid U74006F in the pathogenesis of a murine traumatic shock model. Pentobarbital-anesthetized (40 mg/kg) rats were subjected to Noble-Collip drum trauma and developed a lethal shock state characterized by a decreased mean arterial blood pressure (MABP) to 67 +/- 2 mm Hg and survival time (1.5 +/- 0.2 h). In contrast, sham trauma rats exhibited a MABP of 122 +/- 4 mm Hg at 5 h postanesthesia. Administration of U74006F at doses of 22.5 mg/kg at 15 to 20 min following trauma significantly maintained a higher MABP and prolonged survival compared to those trauma rats receiving only the vehicle for U74006F (0.002 N HCl). U74006F at 15 and 22.5 mg/kg prolonged survival time to 2.6 +/- 0.3 (p less than 0.05) and 3.1 +/- 0.6 h (p less than 0.02), respectively. U74006F also significantly attenuated the plasma accumulation of cathepsin D (p less than 0.02 to p less than 0.01) and free amino-nitrogen compounds (p less than 0.01) compared to the rats receiving only vehicle. Additionally, U74006F at 15 and 22.5 mg/kg blunted the production of the cardiotoxic peptide, myocardial depressant factor (MDF) (p less than 0.01 to p less than 0.001). Moreover, U74006F is a steroid without significant glucocorticoid or mineralocorticoid activity. These results suggest that U74006F may be useful as a therapeutic agent in traumatic shock.
 ...
PMID:Protective effects of a novel nonglucocorticoid 21-aminosteroid (U74006F) during traumatic shock in rats. 168 14

We investigated the effects of a novel, non-glucocorticoid 21-aminosteroid, U74006F, in the pathogenesis of splanchnic artery occlusion (SAO) shock in rats. Pentobarbital-anesthetized (40 mg/kg) rats were subjected to 40 min of occlusion of both the celiac and superior mesenteric arteries followed by reperfusion, which resulted in a severe shock state characterized by a markedly lower mean arterial blood pressure (MABP) and a survival time of 40-80 min post-reperfusion. In contrast, infusion of U74006F (22.5 mg/kg) during the occlusion period resulted in a significantly higher MABP following reperfusion which prolonged survival (117 +/- 3 min vs. 66 +/- 10, P less than .01) compared to those rats receiving only the vehicle for U74006F (0.002 N HCl). Hematocrits measured at the end of each experiment were significantly lower in the treated shock rats compared to the untreated group (55.7 +/- 1.8 vs. 63.0 +/- 1.7, P less than .01). SAO shock rats treated with U74006F also exhibited significantly attenuated plasma accumulation of cathepsin D (P less than .05) and myocardial depressant factor (MDF) (P less than .01). Six of 7 SAO shock rats treated with U74006F survived for 120 min following reperfusion, while none of 7 SAO shock rats given the vehicle survived for 120 min (P less than .01). These results suggest that U74006F has therapeutic utility in SAO shock.
 ...
PMID:Protective effects of a novel 21-aminosteroid during splanchnic artery occlusion shock. 231 Dec 4

A new two-dimensional polyacrylamide gel electrophoresis (PAGE) system with minislab gel apparatus was devised for the rapid (4 h) analysis of peptide fragments derived from the enzymic digestion of myelin basic protein (MBP). The first dimension consisted of 5% polyacrylamide running gels in 1.9 M potassium glycinate, pH 7.3, with 4.3% stacking gels in 0.08 M potassium glycinate, pH 10.3. Anodic and cathodic buffer chambers contained 38 mM glycine/5 mM Tris, pH 8.3, and 10 mM Tris-HCl, pH 8.1, respectively. This system fractionated MBP peptides on the basis of charge. By contrast, acid-urea 15% PAGE separated MBP peptides by both charge and size. A two-dimensional system of 5% PAGE followed by sodium dodecylsulfate 15% PAGE (Laemmli) was used to resolve MBP fragments from pepsin and cathepsin D digests; this analysis indicated that cathodic mobilities could be predicted by the ratio of basic to acidic amino acids in each peptide. This method should be particularly powerful in combination with immunoblotting to identify microheterogenous fragments arising from normal and pathological metabolism of MBP.
 ...
PMID:Two-dimensional electrophoretic characterization of microheterogeneous myelin basic protein fragments. 243 62

A protein solubilized in Tris-HCl/saline buffer from keratinized cells of newborn rat epidermis exhibited inhibitor activity to papain and ficin, but not to trypsin, cathepsin D and pepsin. This protein was purified from keratinized cells as well as nonkeratinized and germinative cells by means of IgG affinity chromatography. The inhibitors extracted from all cell layers were immunologically identical and had a molecular weight of approximately 12,500 +/- 500. Since amino acid analysis showed that the inhibitor contains about 35 residues of glycine per mol, [3H]glycine was used to investigate synthesis of the protein. The inhibitor from nonkeratinized and germinative cells was radioactively labeled by 2 h after injection and appeared in keratinized cells by 48 h after injection. Indirect immunofluorescence microscopy demonstrated in situ distribution of the protein in the entire epidermis, and the protein localized by the plasma membrane in granular cells and diffusely in keratinized cells was shown to be insoluble in Tris-HCl saline buffer. The results indicate that a thiol-proteinase inhibitor is synthesized in epidermal cells during keratinization and is retained as part of the cytoplasmic structure
 ...
PMID:Chemical characterization, synthesis and distribution of proteinase inhibitor in newborn rat epidermis. 615 44

Enzymatic activity was investigated in metal-binding proteins from rat epidermal cells. Tris-HCl buffer soluble and KSCN solubilized proteins were extracted stepwise from granular and cornified cells of 2-day old rat epidermis. Each extract was separately applied to a Cu2+ or Zn2+ chelate Sepharose 6B column and the proteins were eluted with buffers of different pHs and finally with EDTA solution. Metal chelate-binding proteins were found in both soluble and solubilized proteins but there was a larger amount in the latter. Affinity of the proteins to bind with Cu2+ chelate was greater than that with Zn2+ chelate. In Tris-HCl buffer extract, histidase activity was detected in Cu2+ chelate-binding proteins, but not in Zn2+ chelate-binding proteins. Acid phosphatase, cysteine proteinase, dipeptidase, cathepsin D, beta-galactosidase, gelatin hydrolase, and superoxide dismutase did not bind to metal chelates although these enzymes, except acid phosphatase, were inhibited by Cu2+, but not by Zn2+. In contrast, KSCN solubilized metal chelate-binding proteins showed plasminogen activator, acid phosphatase, and gelatin and casein hydrolases while histone hydrolase did not bind to either chelate column. Since metal-binding proteins in rat epidermal cells have been shown previously to be histidine- and cysteine-rich proteins concentrated in keratohyalin granules, interaction of metals and the structural proteins with certain enzymes may be involved in the regulation of epidermal cell functions.
 ...
PMID:Enzymatic activity of metal-binding proteins in epidermal cells. 653 44

Proteolytic modification of circulating insulin-like growth factor binding protein-3 (IGFBP-3) has been described in a number of conditions. Using Western ligand blotting and SDS-PAGE analysis of fragmentation patterns of 125I-labelled IGFBP-3 and 125-labelled IGFBP-1, we have examined conditioned media from cultured human cell lines for the presence of proteolytic activity and compared this with the action of circulating proteases and with characterized enzymes including cathepsin D, kallikrein, plasmin and tissue plasminogen activator. 125I-Labelled IGFBP-3 was incubated with serum from pregnant women, patients following heart surgery and patients with cancer of the breast, lung or head/neck. Following separation of the preincubated samples by SDS-PAGE, a distinct pattern of degradation fragments was observed which was similar in all cases. This proteolytic activity was inhibited in the presence of EDTA, phenanthroline and 4(-2-aminoethyl)-benzenesulphonylfluoride, HCl. These proteases had no detectable effect on IGFBP-1. Serum-free conditioned medium from a human dermal fibroblast cell line, a rabdomyosarcoma, a cervical, a bladder, a chorio- and two-tongue squamous cell carcinoma cell lines all contained proteolytic activity which fragmented IGFBP-3. The pattern of fragments was similar in all cell lines but different from that produced by the circulating proteases. Six out of nine cell lines produced protease(s) which degraded IGFBP-1 in addition to IGFBP-3. Whilst all the characterized enzymes tested also fragmented IGFBP-3 and plasmin cleaved IGFBP-1, none of these acted in the same way as either circulating or cell line-derived proteolytic activity. The activity associated with the characterized enzymes and cell lines was inhibited in the presence of serum from normal healthy subjects. These results demonstrate that the serum of pregnant women, post-operative patients and patients with cancer contain circulating proteases which cause fragmentation of IGFBP-3 but have little effect on IGFBP-1. Cell-derived proteases were shown to act on IGFBP-3 and IGFBP-1 in a number of instances but are not active in the presence of circulating inhibitors. These proteases may play an important role in regulating the availability of IGFs to normal and neoplastic tissues.
 ...
PMID:Proteolytic modification of insulin-like growth factor-binding proteins: comparison of conditioned media from human cell lines, circulating proteases and characterized enzymes. 750 92