Key Spec Table
|Species Reactivity||Key Applications||Host||Format||Antibody Type|
|M, R||IHC, WB||Rb||Purified||Polyclonal Antibody|
|Description||Anti-Cathepsin B Antibody|
|Presentation||Protein A Purified immunoglobulin. 0.1 M Tris-Glycine, 0.15 M NaCl, 0.05% sodium azide, pH 7.4.|
|Application||Anti-Cathepsin B Antibody detects level of Cathepsin B & has been published & validated for use in IH & WB.|
|Safety Information according to GHS|
|Material Size||400 µg|
|Material Package||2 vials of 200 μg|
|Anti-Cathepsin B (rabbit polyclonal IgG) - 1946445||1946445|
|Anti-Cathepsin B (rabbit polyclonal IgG) - 1993906||1993906|
|Anti-Cathepsin B (rabbit polyclonal IgG) - 2197503||2197503|
|Anti-Cathepsin B (rabbit polyclonal IgG) - 2203104||2203104|
|Anti-Cathepsin B (rabbit polyclonal IgG) - 2343121||2343121|
|Anti-Cathepsin B (rabbit polyclonal IgG) - DAM1437120||DAM1437120|
|Anti-Cathepsin B - 0605029340||0605029340|
|Anti-Cathepsin B - 1350293||1350293|
|Anti-Cathepsin B - 14927||14927|
|Anti-Cathepsin B - 23694||23694|
|Reference overview||Application||Pub Med ID|
|Angiogenin secretion from hepatoma cells activates hepatic stellate cells to amplify a self-sustained cycle promoting liver cancer.|
Bárcena, C; Stefanovic, M; Tutusaus, A; Martinez-Nieto, GA; Martinez, L; García-Ruiz, C; de Mingo, A; Caballeria, J; Fernandez-Checa, JC; Marí, M; Morales, A
Scientific reports 5 7916 2015
Hepatocellular carcinoma (HCC) frequently develops in a pro-inflammatory and pro-fibrogenic environment with hepatic stellate cells (HSCs) remodeling the extracellular matrix composition. Molecules secreted by liver tumors contributing to HSC activation and peritumoral stromal transformation remain to be fully identified. Here we show that conditioned medium from HCC cell lines, Hep3B and HepG2, induced primary mouse HSCs transdifferentiation, characterized by profibrotic properties and collagen modification, with similar results seen in the human HSC cell line LX2. Moreover, tumor growth was enhanced by coinjection of HepG2/LX2 cells in a xenograft murine model, supporting a HCC-HSC crosstalk in liver tumor progression. Protein microarray secretome analyses revealed angiogenin as the most robust and selective protein released by HCC compared to LX2 secreted molecules. In fact, recombinant angiogenin induced in vitro HSC activation requiring its nuclear translocation and rRNA transcriptional stimulation. Moreover, angiogenin antagonism by blocking antibodies or angiogenin inhibitor neomycin decreased in vitro HSC activation by conditioned media or recombinant angiogenin. Finally, neomycin administration reduced tumor growth of HepG2-LX2 cells coinjected in mice. In conclusion, angiogenin secretion by HCCs favors tumor development by inducing HSC activation and ECM remodeling. These findings indicate that targeting angiogenin signaling may be of potential relevance in HCC management.
|Increased immunoreactivity of cathepsins in the rat esophagus under chronic acid reflux esophagitis.|
Suyama, M; Koike, M; Asaoka, D; Mori, H; Oguro, M; Ueno, T; Nagahara, A; Watanabe, S; Uchiyama, Y
The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 62 645-60 2014
We have designed a stable rat chronic acid reflux esophagitis (RE) model. In gastrointestinal lesions, several lysosomal cathepsins are known to participate in epithelial permeability in cell-cell connections, such as tight junctions in ulcerative colitis. However, very few studies have focused on the distribution of cathepsins in the esophageal multilayer squamous epithelium. Therefore to clarify the role of cathepsins in RE, we investigated their immunohistological localization in the esophageal epithelium under normal conditions and after RE. Of the cathepsins examined (cathepsins B, C, D, F, H, L, S, and X), granular immunoreactivity for cathepsins B, C, D and L was observed in the control esophageal epithelia; although, their distribution differed depending on the enzyme examined. In the RE model, immunoreactivity of these cathepsins was increased in esophageal epithelial cells and activated macrophages. The immunoreactivity for cathepsins F, H, S and X was barely detectable in the control esophageal epithelium. However, in the RE model, we noticed a slight increase in the expression of cathepsins H and X in the epithelial cells. Furthermore, activated macrophages of the RE model possessed intense immunoreactivity for these cathepsins, which may have been related to esophageal inflammatory mechanisms.
|Streptozotocin-induced diabetes mellitus affects lysosomal enzymes in rat liver.|
Peres, GB; Juliano, MA; Aguiar, JA; Michelacci, YM
Brazilian journal of medical and biological research = Revista brasileira de pesquisas médicas e biológicas / Sociedade Brasileira de Biofísica ... [et al.] 47 452-60 2014
It has been previously shown that dextran sulfate administered to diabetic rats accumulates in the liver and kidney, and this could be due to a malfunction of the lysosomal digestive pathway. The aim of the present study was to evaluate the expression and activities of lysosomal enzymes that act upon proteins and sulfated polysaccharides in the livers of diabetic rats. Diabetes mellitus was induced by streptozotocin in 26 male Wistar rats (12 weeks old), while 26 age-matched controls received only vehicle. The livers were removed on either the 10th or the 30th day of the disease, weighed, and used to evaluate the activity, expression, and localization of lysosomal enzymes. A 50-60% decrease in the specific activities of cysteine proteases, especially cathepsin B, was observed in streptozotocin-induced diabetes mellitus. Expression (mRNA) of cathepsins B and L was also decreased on the 10th, but not on the 30th day. Sulfatase decreased 30% on the 30th day, while glycosidases did not vary (or presented a transitory and slight decrease). There were no apparent changes in liver morphology, and immunohistochemistry revealed the presence of cathepsin B in hepatocyte granules. The decrease in sulfatase could be responsible for the dextran sulfate build-up in the diabetic liver, since the action of sulfatase precedes glycosidases in the digestive pathway of sulfated polysaccharides. Our findings suggest that the decreased activities of cathepsins resulted from decreased expression of their genes, and not from general lysosomal failure, because the levels of glycosidases were normal in the diabetic liver.
|Increased intracranial pressure after diffuse traumatic brain injury exacerbates neuronal somatic membrane poration but not axonal injury: evidence for primary intracranial pressure-induced neuronal perturbation.|
Lafrenaye, AD; McGinn, MJ; Povlishock, JT
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 32 1919-32 2012
Increased intracranial pressure (ICP) associated with traumatic brain injury (TBI) is linked to increased morbidity. Although our understanding of the pathobiology of TBI has expanded, questions remain regarding the specific neuronal somatic and axonal damaging consequences of elevated ICP, independent of its impact on cerebral perfusion pressure (CPP). To investigate this, Fischer rats were subjected to moderate TBI. Measurements of ICP revealed two distinct responses to injury. One population exhibited transient increases in ICP that returned to baseline levels acutely, while the other displayed persistent ICP elevation (greater than 20 mm Hg). Utilizing these populations, the effect of elevated ICP on neuronal pathology associated with diffuse TBI was analyzed at 6 hours after TBI. No difference in axonal injury was observed, however, rats exhibiting persistently elevated ICP postinjury revealed a doubling of neurons with chronic membrane poration compared with rats exhibiting only transient increases in ICP. Elevated postinjury ICP was not associated with a concurrent increase in DNA damage; however, traditional histological assessments did reveal increased neuronal damage, potentially associated with redistribution of cathepsin-B from the lysosomal compartment into the cytosol. These findings indicate that persistently increased ICP, without deleterious alteration of CPP, exacerbates neuronal plasmalemmal perturbation that could precipitate persistent neuronal impairment and ultimate neuronal death.
|Cathepsin B overexpression due to acid sphingomyelinase ablation promotes liver fibrosis in Niemann-Pick disease.|
Moles, A; Tarrats, N; Fernández-Checa, JC; Marí, M
The Journal of biological chemistry 287 1178-88 2012
Niemann-Pick disease (NPD) is a lysosomal storage disease caused by the loss of acid sphingomyelinase (ASMase) that features neurodegeneration and liver disease. Because ASMase-knock-out mice models NPD and our previous findings revealed that ASMase activates cathepsins B/D (CtsB/D), our aim was to investigate the expression and processing of CtsB/D in hepatic stellate cells (HSCs) from ASMase-null mice and their role in liver fibrosis. Surprisingly, HSCs from ASMase-knock-out mice exhibit increased basal level and activity of CtsB as well as its in vitro processing in culture, paralleling the enhanced expression of fibrogenic markers α-smooth muscle actin (α-SMA), TGF-β, and pro-collagen-α1(I) (Col1A1). Moreover, pharmacological inhibition of CtsB blunted the expression of α-SMA and Col1A1 and proliferation of HSCs from ASMase-knock-out mice. Consistent with the enhanced activation of CtsB in HSCs from ASMase-null mice, the in vivo liver fibrosis induced by chronic treatment with CCl(4) increased in ASMase-null compared with wild-type mice, an effect that was reduced upon CtsB inhibition. In addition to liver, the enhanced proteolytic processing of CtsB was also observed in brain and lung of ASMase-knock-out mice, suggesting that the overexpression of CtsB may underlie the phenotype of NPD. Thus, these findings reveal a functional relationship between ASMase and CtsB and that the ablation of ASMase leads to the enhanced processing and activation of CtsB. Therefore, targeting CtsB may be of relevance in the treatment of liver fibrosis in patients with NPD.
|Downregulation of doxorubicin-induced myocardial apoptosis accompanies postnatal heart maturation.|
Shi, J; Zhang, L; Zhang, YW; Surma, M; Mark Payne, R; Wei, L
American journal of physiology. Heart and circulatory physiology 302 H1603-13 2012
Doxorubicin is a highly effective chemotherapeutic agent used for treating a wide spectrum of tumors, but its usage is limited because of its dose-dependent cardiotoxicity, especially in pediatric patients. Accumulating evidence indicates that caspase-dependent apoptosis contributes to the cardiotoxicity of doxorubicin. However, less attention has been paid to the effects of age on doxorubicin-induced apoptosis signaling in myocardium. This study focused on investigating differential apoptotic sensitivity between neonatal and adult myocardium, in particular, between neonatal and adult cardiomyocytes in vivo. Our results show that caspase-3 activity in normal mouse hearts decreased by ≥ 20-fold within the first 3 wk after birth, associated with a rapid downregulation in the expression of key proapoptotic proteins in intrinsic and extrinsic pathways. This rapid downregulation of caspase-3 activity was confirmed by immunostaining for cleaved caspase-3 and terminal deoxynucleotidyl transferase dUTP-mediated nick-end label staining. Doxorubicin treatment induced a dose-dependent increase in caspase-3 activity and apoptosis in neonatal mouse hearts, and both caspase-8 and caspase-9 activations were involved. Using transgenic mice with a nuclear localized LacZ reporter gene to label cardiomyocytes in vivo, we observed a fourfold higher level of doxorubicin-induced cardiomyocyte apoptosis in 1-wk-old mice compared with that in 3-wk-old mice. This study points to a major difference in apoptotic signaling in doxorubicin cardiotoxicity between neonatal and adult mouse hearts and reveals a critical transition from high to low susceptibility to doxorubicin-induced apoptosis during postnatal heart maturation.
|Cathepsin B, cathepsin L, and cystatin C in the porcine uterus and placenta: potential roles in endometrial/placental remodeling and in fluid-phase transport of proteins secreted by uterine epithelia across placental areolae.|
Song G, Bailey DW, Dunlap KA, Burghardt RC, Spencer TE, Bazer FW, Johnson GA
Biol Reprod 82 854-64 Epub 2010 Jan 27 2010
Cathepsins (CTSB and CTSL1) and their inhibitor, cystatin C (CST3), remodel uterine endometrium and placenta for transport of gases, micronutrients, and macromolecules essential for development and growth of the conceptus (embryo/fetus and placental membranes). We examined the temporal/spatial control of expression for CTSB, CTSL1, and CST3 mRNAs in endometria and placentae of pigs using three developmental models: 1) pigs were hysterectomized during the estrous cycle or pregnancy; 2) cyclic pigs were injected with estrogen to induce pseudopregnancy and were hysterectomized; and 3) pigs were ovariectomized, injected with progesterone, and hysterectomized. The abundance of CTSB, CTSL1, and CST3 mRNAs increased in endometrial epithelia during pregnancy and in response to exogenous progesterone but not estrogen. CST3 was also expressed in cells scattered within the stratum compactum stroma. Progesterone decreased epithelial but increased stromal compartment expression of CST3. CTSB increased in all chorionic epithelia, but CTSL1 was limited to chorionic epithelia that form areolae to absorb secretions from uterine glands. Based on the placental and endometrial distribution of CTSL1, we examined expression in the neonatal enterocytes known to transport immunoglobulins from colostrum. CTSL1 was also expressed in enterocytes of intestine from neonatal piglets. Therefore, CTSL1 is expressed by endometrial epithelia, placental areolae, and neonatal intestine, and it may function in the transport of macromolecules across these epithelia. Our results support the idea that reciprocal interactions between CSTL1, CTSB, and CST3 may be required to remodel endometrial and placental tissues for close apposition between maternal and fetal vasculatures and to facilitate transplacental transport of gases, micronutrients (amino acids, glucose), and macromolecules (proteins). Cysteine proteases and their inhibitors may also specifically modify proteins for successful utilization and fluid-phase transport across uterine, placental, and neonatal gut epithelia.
|Effects of long-term progesterone on developmental and functional aspects of porcine uterine epithelia and vasculature: progesterone alone does not support development of uterine glands comparable to that of pregnancy.|
Bailey, DW; Dunlap, KA; Frank, JW; Erikson, DW; White, BG; Bazer, FW; Burghardt, RC; Johnson, GA
Reproduction (Cambridge, England) 140 583-94 2010
In pigs, endometrial functions are regulated primarily by progesterone and placental factors including estrogen. Progesterone levels are high throughout pregnancy to stimulate and maintain secretion of histotroph from uterine epithelia necessary for growth, implantation, placentation, and development of the conceptus (embryo and its extra-embryonic membranes). This study determined effects of long-term progesterone on development and histoarchitecture of endometrial luminal epithelium (LE), glandular epithelium (GE), and vasculature in pigs. Pigs were ovariectomized during diestrus (day 12), and then received daily injections of either corn oil or progesterone for 28 days. Prolonged progesterone treatment resulted in increased weight and length of the uterine horns, and thickness of the endometrium and myometrium. Hyperplasia and hypertrophy of GE were not evident, but LE cell height increased, suggesting elevated secretory activity. Although GE development was deficient, progesterone supported increased endometrial angiogenesis comparable to that of pregnancy. Progesterone also supported alterations to the apical and basolateral domains of LE and GE. Dolichos biflorus agglutinin lectin binding and α(v) integrin were downregulated at the apical surfaces of LE and GE. Claudin-4, α(2)β(1) integrin, and vimentin were increased at basolateral surfaces, whereas occludins-1 and -2, claudin-3, and E-cadherin were unaffected by progesterone treatment indicating structurally competent trans-epithelial adhesion and tight junctional complexes. Collectively, the results suggest that progesterone affects LE, GE, and vascular development and histoarchitecture, but in the absence of ovarian or placental factors, it does not support development of GE comparable to pregnancy. Furthermore, LE and vascular development are highly responsive to the effects of progesterone.
|Vesicular egress of non-enveloped lytic parvoviruses depends on gelsolin functioning.|
Bär, S; Daeffler, L; Rommelaere, J; Nüesch, JP
PLoS pathogens 4 e1000126 2008
The autonomous parvovirus Minute Virus of Mice (MVM) induces specific changes in the cytoskeleton filaments of infected permissive cells, causing in particular the degradation of actin fibers and the generation of "actin patches." This is attributed to a virus-induced imbalance between the polymerization factor N-WASP (Wiscott-Aldrich syndrome protein) and gelsolin, a multifunctional protein cleaving actin filaments. Here, the focus is on the involvement of gelsolin in parvovirus propagation and virus-induced actin processing. Gelsolin activity was knocked-down, and consequences thereof were determined for virus replication and egress and for actin network integrity. Though not required for virus replication or progeny particle assembly, gelsolin was found to control MVM (and related H1-PV) transport from the nucleus to the cell periphery and release into the culture medium. Gelsolin-dependent actin degradation and progeny virus release were both controlled by (NS1)/CKIIalpha, a recently identified complex between a cellular protein kinase and a MVM non-structural protein. Furthermore, the export of newly synthesized virions through the cytoplasm appeared to be mediated by (virus-modified) lysomal/late endosomal vesicles. By showing that MVM release, like entry, is guided by the cytoskeleton and mediated by vesicles, these results challenge the current view that egress of non-enveloped lytic viruses is a passive process.Full Text Article
|Simultaneous human papilloma virus type 16 E7 and cdk inhibitor p21 expression induces apoptosis and cathepsin B activation.|
Kaznelson, DW; Bruun, S; Monrad, A; Gjerløv, S; Birk, J; Röpke, C; Norrild, B
Virology 320 301-12 2004
Human papillomavirus type 16 (HPV-16) is the major risk factor for development of cervical cancer. The major oncoprotein E7 enhances cell growth control. However, E7 has in some reports been shown to induce apoptosis suggesting that there is a delicate balance between cell proliferation and induction of cell death. We have used the osteosarcoma cell line U2OS cells provided with E7 and the cdk2 inhibitor p21 (cip1/waf1) under inducible control, as a model system for the analysis of E7-mediated apoptosis. Our data shows that simultaneous expression of E7 and p21 proteins induces cell death, possibly because of conflicting growth control. Interestingly, E7/p21-induced cell death is associated with the activation of a newly identified mediator of apoptosis, namely cathepsin B. Activation of the cellular caspases is undetectable in cells undergoing E7/p21-induced apoptosis. To our knowledge, this is the first time a role for cathepsin B is reported in HPV-induced apoptotic signalling.