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)

In experimental allergic neuritis (EAN) break-down of myelin is attributed to macrophages, which among other factors contain and secrete proteases. In vitro studies have shown that cathepsin D, an acidic aspartyl endopeptidase, and plasmin can degrade myelin proteins. In order to elucidate a potential therapeutic effect of protease inhibitors we treated Lewis rats, immunized with bovine peripheral nervous system myelin, with epsilon-amino-caproic acid (EACA) or pepstatin. EACA or pepstatin was administered twice daily by intraperitoneal injection beginning on day 6 postimmunization or from the onset of disease (on day 12) through day 24. Compared to saline-treated controls, animals treated with either of the inhibitors showed delayed development of clinical signs and electrophysiological abnormalities. Maximal severity and the further course of disease, however, were not different in control and treated groups. Immunohistological evaluation of sciatic nerve specimens on day 24 postimmunization showed equal numbers of cells positive for ED1 (macrophages) and cathepsin D in all animal groups. There was also no difference in the spontaneous proteolytic activity of the sciatic nerve homogenates at pH 2.8, 5.0, and 7.4. Incubation of the homogenates with pepstatin, however, significantly reduced proteolytic activity at pH 2.8 and 5.0, while EACA had no effect at any pH tested. These results imply that treatment to limit the infiltration of cathepsin D-positive cells or to reduce the induction or activity of cathepsin D may provide a therapeutic avenue for treating inflammatory demyelination of the peripheral nervous system.
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PMID:The use of protease inhibitors in experimental allergic neuritis. 182 13

The early interface reaction of cancellous bone to a nanocrystalline hydroxyapatite (HA) cement containing 3 wt% collagen type I (HA/Coll) with a setting under physiological temperature and pH was observed using immunohistochemical techniques. Pure HA served as a control. Cylinders with a diameter of 2 mm were implanted into the proximal tibia of 72 adult Wistar rats. Histological sections of 6 animals were prepared after 1, 2, 4, 6, 14 and 28 days. First, osteoblast-like cells as well as a marked reaction for osteonectin, osteopontin and its ligand CD44 were observed as early as 2 days after implantation at the interface around HA/Coll implants. Further, reactivity for ED1 and cathepsin D, both markers for phagocytotic cells, appeared earlier and stronger around HA/Coll. In cell counts, a significantly higher average number of ED1- and cathepsin D-positive phagocytotic cells was observed around the HA/Coll implants on days 6 (p < 0.01), 14 and 28 (p < 0.05). The number of osteopontin-positive cells was significantly higher around HA/Coll implants at days 6 and 14 (p < 0.05). Two weeks after the implantation, first islands of newly formed woven bone were observed around the HA/Coll implant, but not around the control implant. The amount of direct bone contact after 28 days averaged 28% around pure HA and 51% around HA/Coll implants (p < 0.05). While both implants displayed a good osteoconductivity, a higher bone remodelling activity was observed around collagen-containing HA implants compared to pure HA implants. It appears that the addition of collagen to HA implants can enhance both phagocytotic and osteogenic processes. This may result in an earlier acceptance and better osseointegration of the HA/Coll implants into the surrounding tissue.
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PMID:Collagen type I increases bone remodelling around hydroxyapatite implants in the rat tibia. 1565 32

The effect of osteocalcin (OC), an extracellular bone matrix protein, on bone healing around hydroxyapatite/collagen composites was investigated. Cylindrical nanocrystalline hydroxyapatite implants of 2.5-mm diameter containing 2.5% biomimetically mineralized collagen type I were inserted press-fit into the tibial head of adult Wistar rats. To one implant group, 10 mug/g OC was added. Six specimens per group were analyzed at 2, 7, 14, 28, and 56 days. After 14 days, newly formed woven bone had reached the implant surface of the OC implants whereas a broad fibrous interface could still be observed around controls. Woven bone was formed directly around both implant groups after 28 days and had been replaced partially by lamellar bone around the OC implants only. No significant differences in total bone contact were seen between both groups after 56 days. The higher number of phagocytosing cells and osteoclasts characterized immunohistochemically with ED1, cathepsin D, and tartate-resistant alkaline phosphatase around the OC implants at the early stages of bone healing suggests an earlier onset of bone remodeling. The earlier and increased expression of bone-specific matrix proteins and multifunctional adhesion proteins (osteopontin, bone sialoprotein, CD44) at the interface around the OC implants indicates that OC may accelerate bone formation and regeneration. This study supports the observations from in vitro studies that OC activates both osteoclasts and osteoblasts during early bone formation.
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PMID:Osteocalcin enhances bone remodeling around hydroxyapatite/collagen composites. 1580 Aug 55

To investigate the involvement of flotillin-1 in acute experimental testicular torsion, we examined the expression and cellular localization of flotillin-1 and cathepsin D in the rat testis with ischemia/reperfusion (I/R) injury. Western blot analysis showed that the expression of flotillin-1 increased significantly 6h after I/R and that the level remained elevated for 48 h. Immunohistochemically, flotillin-1 was constitutively localized in some Sertoli cells, peritubular myoid cells, and interstitial cells in the normal testis. After I/R injury, Sertoli cells in the damaged tubules were intensely immunostained for flotillin-1 at 24 and 48 h after I/R. Flotillin-1 was also detected in some inflammatory cells in the interstitial space around damaged tubules. Furthermore, flotillin-1 was colocalized with cathepsin D, a lysosomal marker, in normal testis (mainly in Sertoli cells), and the colocalization was greater in Sertoli cells and macrophages in I/R injured testes. Therefore, we postulate that flotillin-1 immunoreactivity is increased in some Sertoli and inflammatory cells (especially in ED1-positive activated macrophages) in testicular torsion and that flotillin-1 in the injured testis associates with lysosomes in Sertoli cells and macrophages, activating subsequent signals in inflammatory macrophages and Sertoli cells after I/R.
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PMID:Immunohistochemical study of flotillin-1 in rat testis with ischemia/reperfusion injury. 1721 21