Buy our Natural human Cathepsin D protein. Ab91123 is an active full length protein produced in Nativesyntheticaly and has been validated in WB, FuncS…
TY - JOUR. T1 - Effects of insulin on protein degradation and lysosomal cathepsin D in perfused skeletal muscle. AU - Li, J. B.. AU - Rannels, S. R.. AU - Burkart, M. E.. AU - Jefferson, L. S.. PY - 1975/1/1. Y1 - 1975/1/1. UR - http://www.scopus.com/inward/record.url?scp=0016610685&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0016610685&partnerID=8YFLogxK. M3 - Article. AN - SCOPUS:0016610685. VL - 34. SP - No.654. JO - Federation Proceedings. JF - Federation Proceedings. SN - 0014-9446. IS - 3. ER - ...
Mutants of Caenorhabditis elegans having about 10% of wild-type activity of the aspartyl protease cathepsin D have been isolated by screening. Mutant homozygotes have normal growth rates and no obvious morphological or developmental abnormalities. The mutant gene (cad-1) has been mapped to the right extremity of linkage group II. Heterozygous animals (cad-1/+) show intermediate enzyme levels and animals heterozygous for chromosomal deficiencies of the right extremity of linkage group II have 50% of wild-type activity. Cathepsin D purified from a mutant strain has a lower activity per unit mass of pure enzyme. These data suggest that cad-1 is a structural gene for cathepsin D. ...
rat Cathepsin D/CTSD gene cDNA, cloning vector & expression plasmid, mutiple tags. Optimized for high expression in mammalian cells. Save up to 60%.
Order Cathepsin D ELISA Kits for many Reactivities. Chicken, Cow, Dog and more. Compare Cathepsin D ELISA Kits and find the right product on antibodies-online.com.
Conner, G.E. (1989). „Isolation of procathepsin D from mature cathepsin D by pepstatin affinity chromatography. Autocatalytic proteolysis of the zymogen form of the enzyme". Biochem. J. 263: 601-604. PMID 2512908 ...
Cathepsin D小鼠单克隆抗体[CTD-19](ab6313)可与小鼠, 人样本反应并经WB, IP, ELISA, IHC, ICC/IF实验严格验证,被13篇文献引用并得到14个独立的用户反馈。
A novel combinatorial mutagenesis strategy (shuffle mutagenesis) was developed to identify sequences in the propiece and amino lobe of cathepsin D which direct oligosaccharide phosphorylation by UDP-GlcNAc:lysosomal enzyme N-acetylglucosamine 1-phosphotransferase. Propiece restriction fragments and oligonucleotide cassettes corresponding to 13 regions of the cathepsin D and glycopepsinogen amino lobes were randomly shuffled together to generate a large library of chimeric molecules. The library was inserted into an expression vector encoding the carboxyl lobe of cathepsin D with a carboxyl-terminal myc epitope and a CD8 transmembrane extension. Transfected COS1 cells expressing the membrane-anchored forms of the cathepsin D/glycopepsinogen chimeras at the cell surface were selected with solid phase mannose 6-phosphate receptor or an antibody to the myc epitope. Plasmids were rescued in Escherichia coli and sequenced by hybridization to the original oligonucleotide cassettes. Two regions of the cathepsin
This gene encodes a lysosomal aspartyl protease composed of a dimer of disulfide-linked heavy and light chains, both produced from a single protein precursor. This proteinase, which is a member of the peptidase C1 family, has a specificity similar to but narrower than that of pepsin A. Transcription of this gene is initiated from several sites, including one which is a start site for an estrogen-regulated transcript. Mutations in this gene are involved in the pathogenesis of several diseases, including breast cancer and possibly Alzheimer disease. [provided by RefSeq, Jul 2008]
The microenvironment that surrounds tumor cells is characterized by hypoxic conditions and extracellular acidity. These hostile conditions induce crucial changes in cell behavior and can promote the secretion of many soluble factors such as growth factors, cytokines and enzymes. The lysosomal aspartyl-endopeptidase cathepsin D (CD) is a marker of poor prognosis in breast cancer and is associated with a metastatic risk. In this study, the transport of CD was investigated in a model of breast cancer cells line (MCF-7) cultivated under hypoxia and acidification of media. CD secretion was assessed using Western blot analysis and protease activity was measured in conditioned culture media. We demonstrate that cultured MCF-7 cells secrete an active 52 kDa pCD precursor and report that under hypoxia there was an increased amount of pCD secreted. More surprisingly, extracellular acidification (pH 6 and 5.6) induced the secretion of the fully-mature and active (34 kDa + 14 kDa) double chain CD. Our findings
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
1LYB: Crystal structures of native and inhibited forms of human cathepsin D: implications for lysosomal targeting and drug design.
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a Immunoblotting analysis of proteins in extract of humanized liver tissues that bind to biotinylated LINC01018 or a control using an anti-HuR antibody. b Left, anti-HuR immunoblotting analysis of proteins in immunoprecipitates of humanized liver tissues using an anti-HuR antibody. Right, Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and LINC01018 RNA levels in immunoprecipitates of humanized liver tissues using an anti-HuR antibody. c. Expression levels of human HuR and LINC01018 target genes in the livers of control (LacZ sh, n = 5) and HuR KD (HuR sh, n = 6) humanized mice after a 24 h food withdrawal. d Gene expression in livers of humanized mice receiving both control (LacZ shRNA) and HuR KD, or LINC01018 KD and HuR KD adenoviruses (n = 7 for each group). e Gene expression in livers of wild-type mice receiving control (LacZ shRNA) or mouse HuR KD adenoviruses (n = 6 for each group). f Gene expression in livers of wild-type mice receiving control or LINC01018 overexpression (OE) ...
Rabbit polyclonal Cathepsin D antibody validated for WB, ELISA, IHC, ICC/IF and tested in Human. Referenced in 1 publication and 1 independent review…
(A) Schematic presentation of CatD promoter region. The TATA and GC sequences are represented by square boxes, five transcription start sites are indicated by a
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
In a preceding study we have described the development of a new hydroxyethylene (HE) core motif displaying P1 aryloxymethyl and P1 methoxy substituents delivering potent BACE-1 inhibitors. In a continuation of this work we have now explored the SAR of the S1 pocket by introducing a set of P1 alkoxy groups and evaluated them as BACE-1 inhibitors. Previously the P1 and P1 positions of the classical HE template have been relatively little explored due to the complexity of the chemical routes involved in modifications at these positions. However, the chemistries developed for the current HE template renders substituents in both the P1 and P1 positions readily available for SAR exploration. The BACE-1 inhibitors prepared displayed IC50 values in the range of 4-45 nM, where the most potent compounds featured small P1 groups. The cathepsin D selectivity which was high for the smallest P1 sustituents (P1=ethoxy, fold selectively ,600) dropped for larger groups (P1=benzyloxy, fold selectivity of ...
Background. Lysosomal enzymuria is usually considered to be a non-specific marker of renal injury, but little is known about lysosomal enzyme excretion in renal proximal tubular cell disorders such as the renal Fanconi syndrome (FS). We examined excretion of two lysosomal enzymes and the cation-independent mannose-6-phosphate receptor (CI-MPR) in patients with inherited FS.. Methods. The lysosomal enzyme cathepsin D was measured by ELISA and isolated by pepstatin-agarose affinity chromatography; N-acetyl-β-d-glucosaminidase (NAG) was assayed colorimetrically, as was the cytosolic enzyme lactate dehydrogenase (LDH). Cathepsin D, procathepsin D and CI-MPR were also detected by western blotting. No patient had a serum creatinine concentration ,170 μmol/L. Soluble CI-MPR, isolated from fetal calf serum and bound to agarose, was used to probe cathepsin D for mannose-6-phosphate (M6P).. Results. Increased excretion of cathepsin D (mean = 44-fold) and NAG (mean = 12-fold) was found in FS patients: ...
Immunohistochemical distributions of cathepsins D and E were determined in normal mucosa, metaplastic, dysplastic, and cancerous lesions of the human stomach. Cathepsins D and E were localised in the foveolar epithelium and parietal cells of the normal gastric mucosa, but their intracytoplasmic distributions were different - cathepsin E distribution was even and diffuse in the cytoplasm while cathepsin D was found in coarse intracytoplasmic granules. Chronic inflammation and ulcer did not influence the distribution of these enzymes. No positive staining was obtained in the incomplete type of intestinal metaplasia, dysplasia, and well differentiated adenocarcinoma. Tumour cells of signet ring cell carcinoma and poorly differentiated adenocarcinoma cells, however, gave strong and diffuse stainings for cathepsins D and E in the cytoplasm. The results suggest that the distribution of cathepsins D and E is related to each specialised function of the foveolar epithelium and the parietal cells, and ...
Apoptosis was inhibited in rat cardiomyocytes pretreated with the aspartic protease inhibitor pepstatin A and subsequently exposed to naphthazarin (5,8-dihydroxy-1,4-naphthoquinone). Cathepsin D was released from lysosomes to the cytosol upon exposure to naphthazarin, and the enzyme activity decreased simultaneously. Later, cathepsin D reappeared in granules of increased size, and enzyme activity was restored. Activation of caspase-3- like proteases was detected, and the number of cells showing apoptotic morphology increased with time. Pepstatin A pretreatment did not prevent release of cathepsin D from lysosomes but did significantly inhibit subsequent naphthazarin-induced caspase activation and apoptotic morphology. This suggests that cathepsin D exerts its apoptosis-stimulating effect upstream of caspase-3-like activation. (C) 2000 Academic Press.. ...
The purification of cathepsin D from pig uterus by two-step affinity chromatography on concanavalin A- and pepstatin-Sepharose was described previously [Afting & Becker (1981) Biochem. J. 197, 519-522]. In this paper, chemical and physical properties of the proteinase are presented. The purified enzyme showed three bands on SDS (sodium dodecyl sulphate)/polyacrylamide-gel electrophoresis, one main band corresponding to an Mr of 31 000 and two minor bands with Mr values of 43 000 and 15 000 respectively. Gel filtration on Bio-gel P-150 and sedimentation-diffusion equilibrium studies give an Mr for the main band of about 35 000. The pI of the enzyme was determined to be 7.2. Haemoglobin was the best substrate, with a Km value of 6.4 X 10(-6)M. It was hydrolysed with a pH optimum between 3.0 and 3.3 for a substrate concentration of 100 microM. The proteinase was stable over the pH range of 3.5-6.5. At pH 6 the enzyme showed stability up to a temperature of 50 degrees C; at pH 3 the activity was ...
Calpains regulate activation of Bax and cathepsin D in vivo. (A-C) Representative images of immunofluorescence analysis of retinas after mock intravitreal injection or injection of calpastatin in P11 rd1 (A), P10 P23HTg (B), and P45 Rho−/− (C) mice. Upper parts of figure are stained with an activated Bax-specific antibody (red), and nuclei are stained in blue with DAPI. Lower parts of figure are images of calpain activity assay (blue). Vertical white lines indicate the layer of photoreceptor cells; n = 3. Scale bar for all figure parts is shown at upper left (A) and is 10 μm. (D-F) Western blotting of cathepsin D in total protein extracts from P11 rd1 (D), P10 P23HTg (E), and P45 Rho−/− (F) either mock injected or injected with calpastatin (CS). The antibody recognizes both cathepsin D (46 kDa) and activated cathepsin D (32 kDa). Normalization was performed with anti-actin antibodies (lower). Molecular weights are shown in kDa. (G) Quantification by densitometry of Western blotting ...
In contrast to the studies of breast tumor biospies, proteomic analysis starting from breast cancer cells in culture has already given significant results with the identification of proteins with clinical interest. In 1980, Westley and Rochefort identified a secreted 46-kDa glycoprotein, induced by estrogens in human breast cancer cell lines, that was identified with specific antibodies as being the protease cathepsin D (22). In 1989, a computer-based analysis of 2DE gels reported a total of eight polypeptide differences between cancerous and normal breast epithelial cells in tissue culture (23). More precise characterization of such polypeptide differences was published in the early 90s with the demonstration that normal breast epithelial cells produce keratins K5, K6, K7, and K17, whereas tumor cells produce mainly keratins K8, K18, and K19 (24). This distribution was secondarily confirmed in tumor samples (25), and cytokeratin immunodetection is now eventually used to help discriminate benign ...
TY - JOUR. T1 - Proteolysis regulates exposure of the IIICS-1 adhesive sequence in plasma fibronectin. AU - Ugarova, Tatiana. AU - Ljubimov, Alexander V.. AU - Deng, Lynn. AU - Plow, Edward F.. PY - 1996. Y1 - 1996. N2 - The alternatively spliced type III connecting segment (IIICS) of fibronectin (Fn) contains an amino acid sequence, CS-1, which is recognized by the integrin receptor, α4β1. Plasma Fn inhibits α4β1-dependent binding of lymphocytes and monocytes to CS-1 containing Fn derivatives poorly, suggesting limited exposure of the CS-1 sequence in Fn. To test the availability of CS-1 in plasma Fn, an antibody was raised to the synthetic peptide CS-1. The CS-1 sequence was found to be minimally exposed in plasma Fn: and immobilization of Fn, a model of matrix deposition, caused only a modest increase in its exposure. Digestion of Fn with selected proteases, however, induced substantial expression of the CS-1 sequence. The acid protease cathepsin D generated fragments of 31-33.5 kDa from ...
Diabetic (DM) patients have exacerbated atherosclerosis and high CVD burden. Changes in lipid metabolism, lipoprotein structure, and dysfunctional HDL are characteristics of diabetes. Our aim was to investigate whether serum ApoA-I, the main protein in HDL, was biochemically modified in DM patients. By using proteomic technologies, we have identified a 26 kDa ApoA-I form in serum. MS analysis revealed this 26 kDa form as a novel truncated variant lacking amino acids 1-38, ApoA-IΔ(1-38). DM patients show a 2-fold increase in ApoA-IΔ(1-38) over nondiabetic individuals. ApoA-IΔ(1-38) is found in LDL, but not in VLDL or HDL, with an increase in LDL3 and LDL4 subfractions. To identify candidate mechanisms of ApoA-I truncation, we investigated potentially involved enzymes by in silico data mining, and tested the most probable molecule in an established animal model of diabetes. We have found increased hepatic cathepsin D activity as one of the potential proteases involved in ApoA-I truncation. ...
is one of the three main causative agents of human schistosomiasis, a major health problem with a vast socio-economic impact. Recent advances in the proteomic analysis of schistosomes have revealed that peptidases are the main virulence factors involved in the pathogenesis of this disease. In this context, evolutionary studies can be applied to identify peptidase families that have been expanded in genomes over time in response to different selection pressures. Using a phylogenomic approach, we searched for expanded endopeptidase families in the S. mansoni predicted proteome with the aim of contributing to the knowledge of such enzymes as potential therapeutic targets. We found three endopeptidase families that comprise leishmanolysins (metallopeptidase M8 family), cercarial elastases (serine peptidase S1 family) and cathepsin D proteins (aspartic peptidase A1 family). Our results suggest that the Schistosoma members of these families originated from successive gene duplication events in the ...
htr1d gene expression in Bgee. Bgee allows to automatically compare gene expression patterns between species, by referencing expression data on anatomical ontologies, and designing homology relationships between them.
Benes P., Vashishta A., Saraswat-Ohri S., Fusek M., Pospisilova S., Tichy B., Vetvicka V.: Effect of procathepsin D activation peptide on gene expression of breast cancer cells. Cancer Lett., 2005, E-pub Sep 13. IF 2,9382.
View Hps3/Hps3 Myo5a/Myo5a Mreg/Mreg involves: C57BL/10J: phenotypes, images, diseases, and references.
Human 17beta-hydroxysteroid dehydrogenase type 1 (17β-HSD1) is a steroid-converting enzyme that has long been known to play critical roles in estradiol synthesis and more recently in dihydrotestosterone (DHT) inactivation, showing a dual function that promotes breast cancer cell proliferation. Previously, we reported the first observation of the influence of the enzyme on endogenous estrogen-responsive gene expression. Here, we demonstrate the impact of 17β-HSD1 expression on the breast cancer cell proteome and investigate its role in cell migration. 17β-HSD1 was stably transfected in MCF7 cells and the proteome of the generated cells overexpressing 17β-HSD1 (MCF7-17βHSD1 cells) was compared to that of the wild type MCF7 cells. Proteomics study was performed using two-dimensional gel electrophoresis followed by mass spectrometry analysis of differentially expressed protein spots. Reverse transcription quantitative real-time PCR (RT-qPCR) was used to investigate the transcription of individual gene.
Zhou X, Sullivan P, Sun L, Hu F The interaction between progranulin and prosaposin is mediated by granulins and the linker region between saposin B and C. Journal of Neurochemistry 2017 June 22.. Zhou X, Sun L, Bracko O, Choi JW, Jia Y, Nana AL, Brady OA, Hernandez JCC, Nishimura N, Seeley WW, & Hu F. Impaired prosaposin lysosomal trafficking in frontotemporal lobar degeneration due to progranulin mutations. Nature Communications 2017 May 25.. Zhou X, Paushter DH, Feng T, Pardon CM, Mendoza CS, Hu F. Regulation of cathepsin D activity by the FTLD protein progranulin. Acta Neuropathologica. Epub ahead of print. 2017 May 10.. Zhou X, Sun L, Brady OA, Murphy KA, Hu F. Elevated TMEM106B levels exaggerate lipofuscin accumulation and lysosomal dysfunction in aged mice with progranulin deficiency. Acta Neuropathologica Communications. 2017 Jan 26;5(9).. Sullivan PM, Zhou X, Robins AM, Paushter DH, Kim D, Smolka MB, Hu F. The ALS/FTLD associated protein C9orf72 associates with SMCR8 and WDR41 to ...
Currently there are no approved biomarkers for the pre-symptomatic diagnosis of Alzheimers disease (AD). Cathepsin-D (Cat-D) is a lysosomal protease that is present at elevated levels in amyloid plaques and neurons in patients with AD and is also elevated in some cancers. We have developed a magnetic resonance imaging (MRI)/fluorescent contrast agent to detect Cat-D enzymatic activity. The purpose of this study was to investigate the cellular and tissue uptake of this MRI/fluorescent contrast agent. The agent consists of an MRI probe [DOTA-caged metal ion (Gd3+ or Tm3+)] and a fluorescent probe coupled to a cell-penetrating-peptide sequence by a Cat-D recognition site. The relaxivity of Gd3+-DOTA-CAT(cleaved) was measured in 10% heat-treated bovine serum albumin (BSA) phantoms to assess contrast efficacy at magnetic fields ranging from 0.24 mT to 9.4 T. In vitro, Tm3+-DOTA-CAT was added to neuronal SN56 cells over-expressing Cat-D and live-cell confocal microscropy was performed at 30 min. ...
To investigate the role of newly synthesized proteins during autophagic sequestration and degradation, the effects of protein synthesis inhibition on autophagic vacuole (AV) formation and degradation were analyzed. The inhibition of protein synthesis was found to separate autophagic sequestration from the delivery of lysosomal enzymes to (AVs). Pretreatment with cycloheximide for , or = 3 h caused a drastic inhibition of autophagy-induced degradation. Surprisingly, morphological analyses showed that the inhibition of protein synthesis for up to 12 h did not block the formation of nascent AVs; however, it did prevent their conversion into degradative AVs. Using immunoperoxidase cytochemistry with an antibody against cathepsin D and labeling of lysosomes with endocytosed colloidal gold, we found that the nascent AVs that formed during prolonged cycloheximide pretreatment had not received lysosomal markers. The inhibition of autophagic degradation and lysosomal enzyme delivery were rapidly reversed ...
gp120 is a subunit of the envelope glycoprotein of HIV-1. The third variable loop region of gp120 (V3 loop) contains multiple immunodominant epitopes and is also functionally important for deciding cell-tropism of the virus. 447-52D is a monoclonal antibody that recognizes the conserved tip of the V3 loop in a β-turn conformation. This antibody has previously been shown to neutralize diverse strains of the virus. In an attempt to generate an immunogen competent to generate 447-52D-like antibodies, the known epitope of 447-52D was inserted at three different surface loop locations in the small, stable protein Escherichia coli Trx (thioredoxin). At one of the three locations (between residues 74 and 75), the insertion was tolerated, the resulting protein was stable and soluble, and bound 447-52D with an affinity similar to that of intact gp120. Upon immunization, the V3 peptide-inserted Trx scaffold was able to generate anti-V3 antibodies that could compete out 447-52D binding to gp120. Epitope ...
Proteomics and at least one of the other two approaches identified a molecular signature of plaques from symptomatic patients that comprised matrix metalloproteinase 9, chitinase 3-like-1, S100 calcium binding protein A8 (S100A8), S100A9, cathepsin B, fibronectin, and galectin-3-binding protein. Biomarker candidates measured in 685 subjects in the Bruneck study were associated with progression to advanced atherosclerosis and incidence of cardiovascular disease over a 10-year follow-up period. A 4-biomarker signature (matrix metalloproteinase 9, S100A8/S100A9, cathepsin D, and galectin-3-binding protein) improved risk prediction and was successfully replicated in an independent cohort, the SAPHIR study.. ...
Proteomics and at least one of the other two approaches identified a molecular signature of plaques from symptomatic patients that comprised matrix metalloproteinase 9, chitinase 3-like-1, S100 calcium binding protein A8 (S100A8), S100A9, cathepsin B, fibronectin, and galectin-3-binding protein. Biomarker candidates measured in 685 subjects in the Bruneck study were associated with progression to advanced atherosclerosis and incidence of cardiovascular disease over a 10-year follow-up period. A 4-biomarker signature (matrix metalloproteinase 9, S100A8/S100A9, cathepsin D, and galectin-3-binding protein) improved risk prediction and was successfully replicated in an independent cohort, the SAPHIR study.. ...
Hookworm filariform Ac-APR -1 is a cathepsin D aspartic protease from A. caninum which initiates digestive cascade ⇒ If you can block this activity it should
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Acts as component of the GARP complex that is involved in retrograde transport from early and late endosomes to the trans-Golgi network (TGN). The GARP complex is required for the maintenance of the cycling of mannose 6-phosphate receptors between the TGN and endosomes, this cycling is necessary for proper lysosomal sorting of acid hydrolases such as CTSD (PubMed:18367545). Within the GARP complex, required to tether the complex to the TGN. Not involved in endocytic recycling (PubMed:25799061 ...
Pepstatin is a strong inhibitor for all acid proteases. It does not inhibit other groups of proteases, such as the neutral and alkaline proteases (1). The unusual potency of pepstatin toward acid prot
Well he made it to Cat C and repeated a few times before really nailing it. At that moment I thought I might have made the right decision to go forward with him. Great video and a smile ear to ear made us go back up for a Cat D. The dive went okay better than some, it was landing that went a bit haywire. He flew a nice patern into the wind and at flare time only went to his shoulders and in his words. "froze". He did PLF but hit rather hard. He and I knew he injured himself. A week later now he has pins in his pelvis from 4 fractures. Again, he didnt hit all that hard but his age probably was a severe factor. I have seen him several times now and he is still motivated but it looks like a long recovery for him ...
INRA Constellation of Experimental Watersheds: Cyberinfrastructure to Support Publication of Water Resources Data, J. S. Horsburgh, David G. Tarboton, K. Schreuders, D. P. Ames, J. P. McNamara, L. A. Marshall, B. L. McGlynn, D. L. Kane, A. Tidwell, J. Boll, N. W. Hinman, and M. E. Barber; Eos. Trans. AGU. ...
Neutrophils undergo rapid constitutive apoptosis that is accelerated following bacterial ingestion as part of effective immunity, but is also accelerated by bacterial exotoxins as a mechanism of immune evasion. The paradigm of pathogen-driven neutrophil apoptosis is exemplified by the Pseudomonas aeruginosa toxic metabolite, pyocyanin. We previously showed pyocyanin dramatically accelerates neutrophil apoptosis both in vitro and in vivo, impairs host defenses, and favors bacterial persistence. In this study, we investigated the mechanisms of pyocyanin-induced neutrophil apoptosis. Pyocyanin induced early lysosomal dysfunction, shown by altered lysosomal pH, within 15 min of exposure. Lysosomal disruption was followed by mitochondrial membrane permeabilization, caspase activation, and destabilization of Mcl-1. Pharmacological inhibitors of a lysosomal protease, cathepsin D (CTSD), abrogated pyocyanin-induced apoptosis, and translocation of CTSD to the cytosol followed pyocyanin treatment and ...
In many cases, apoptosis may be initiated by a minor lysosomal destabilization, which some time later is followed by a secondary, more pronounced, lysosomal rupture. After exposure to low concentrations of sphingosine, a lysosomotropic detergent, Jurkat and J774 cells underwenr apoptotic cell death, while cells exposed to higher concentrations of this agent showed necrosis. Sphingosine-induced apoptosis was partly prevented by the inhibitors of lysosomal aspartic or cysteine proteases, pepstatin A or E64d. Under these conditions, caspase-3 like activity was reduced 40-55%, suggesting that lysosomal enzymes could be upstream activators of caspase-3.. In J774 cells over-expressing Bcl-2, the early oxidant-induced lysosomal destabilization takes place, but the delayed secondary lysosomal rupture and ensuing apoptosis are both suppressed. Phosphorylation of Bcl-2 seems to be required for this anti-apoptotic effect because the protection is amplified by pre-treatment with phorbol 12-myristate ...
Publisher: University of Delaware. Date Issued: 2014. Abstract: This study was designed to examine the mechanism by which inhibition of lysosomal proteases causes cell death in neuroblastoma. The major lysosomal proteases are two cysteine proteases, cathepsins B and L, and an aspartic protease, cathepsin D. Inhibition of these three proteases was found to cause cellular accumulation of fragments of the IGF-1 receptor. The fragments were located in dense organelles that were characterized as autophagosomes. This novel discovery provides the first clear link between lysosIGF-1omal function, autophagy and IGF-1 mediated cell proliferation. It provides a mechanistic explanation for enhanced cytotoxicity of chemotherpautic agents when combined with inhibitors of lysosomal function and autophagy. A more in depth analysis of the IGF1 signaling pathway revealed that the MAPK pathway was particularly impaired in inhibitor treated cells, while the PKB cell survival pathway remained functional. It was ...
We synthesized one series of fluorogenic substrates for cathepsin B derived from the peptide Bz-F-R-MCA (Bz = benzoyl, MCA = 7-methyl-coumarin amide) substituting Phe at the P(2) position by non-natural basic amino acids that combine a positively charged group with aromatic or aliphatic radicals at the same side chain, namely, 4-aminomethyl-phenylalanine, 4-guanidine-phenylalanine. 4-aminomethyl-N-isopropyl-phenylalanine. 3-pyridyl-alanine, 4-piperidinyl-alanine, 4-amino-methyl-cyclohexyl-alanine. 4-aminocyclohexyl-alanine, and N(im)-dimethyl-histidine. Bz-F-R-MCA was the best substrate for cathepsin B but also hydrolyzed Bz-R-R-MCA with lower efficiency, since the protease accepts Arg at St due to the presence of Glu(245) at the bottom of this subsite. the presence of the basic non-natural amino acids at the Pt position of the substrate partially restored the catalytic efficiency of cathepsin B. All the kinetic parameters for hydrolysis of the peptides described in this paper are in accordance ...
Cathepsin L antibody [2H7] (cathepsin L1) for ELISA, WB. Anti-Cathepsin L mAb (GTX50040) is tested in Human samples. 100% Ab-Assurance.