Calpain: Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including NEUROPEPTIDES; CYTOSKELETAL PROTEINS; proteins from SMOOTH MUSCLE; CARDIAC MUSCLE; liver; platelets; and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. This enzyme was formerly listed as EC 3.4.22.4.Dipeptides: Peptides composed of two amino acid units.Cysteine Proteinase Inhibitors: Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.Calcium-Binding Proteins: Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS.AcrylatesSpectrin: A high molecular weight (220-250 kDa) water-soluble protein which can be extracted from erythrocyte ghosts in low ionic strength buffers. The protein contains no lipids or carbohydrates, is the predominant species of peripheral erythrocyte membrane proteins, and exists as a fibrous coating on the inner, cytoplasmic surface of the membrane.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Leupeptins: A group of acylated oligopeptides produced by Actinomycetes that function as protease inhibitors. They have been known to inhibit to varying degrees trypsin, plasmin, KALLIKREINS, papain and the cathepsins.Muscular Dystrophies, Limb-Girdle: A heterogenous group of inherited muscular dystrophy that can be autosomal dominant or autosomal recessive. There are many forms (called LGMDs) involving genes encoding muscle membrane proteins such as the sarcoglycan (SARCOGLYCANS) complex that interacts with DYSTROPHIN. The disease is characterized by progressing wasting and weakness of the proximal muscles of arms and legs around the HIPS and SHOULDERS (the pelvic and shoulder girdles).Talin: A 235-kDa cytoplasmic protein that is also found in platelets. It has been localized to regions of cell-substrate adhesion. It binds to INTEGRINS; VINCULIN; and ACTINS and appears to participate in generating a transmembrane connection between the extracellular matrix and the cytoskeleton.Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.Databases, Protein: Databases containing information about PROTEINS such as AMINO ACID SEQUENCE; PROTEIN CONFORMATION; and other properties.Sequence Analysis, Protein: A process that includes the determination of AMINO ACID SEQUENCE of a protein (or peptide, oligopeptide or peptide fragment) and the information analysis of the sequence.Systems Integration: The procedures involved in combining separately developed modules, components, or subsystems so that they work together as a complete system. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Internet: A loose confederation of computer communication networks around the world. The networks that make up the Internet are connected through several backbone networks. The Internet grew out of the US Government ARPAnet project and was designed to facilitate information exchange.Proteome: The protein complement of an organism coded for by its genome.Encyclopedias as Topic: Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)Hydrogen-Ion Concentration: The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Cysteine Proteases: A subclass of peptide hydrolases that depend on a CYSTEINE residue for their activity.Peptide Hydrolases: Hydrolases that specifically cleave the peptide bonds found in PROTEINS and PEPTIDES. Examples of sub-subclasses for this group include EXOPEPTIDASES and ENDOPEPTIDASES.Cysteine Dioxygenase: An enzyme that catalyzes the conversion of L-CYSTEINE to 3-sulfinoalanine (3-sulfino-L-alanine) in the CYSTEINE metabolism and TAURINE and hypotaurine metabolic pathways.Cysteine: A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.Helminth Proteins: Proteins found in any species of helminth.Sex Determination Processes: The mechanisms by which the SEX of an individual's GONADS are fixed.Sex Determination Analysis: Validation of the SEX of an individual by inspection of the GONADS and/or by genetic tests.Caenorhabditis elegans: A species of nematode that is widely used in biological, biochemical, and genetic studies.Caenorhabditis elegans Proteins: Proteins from the nematode species CAENORHABDITIS ELEGANS. The proteins from this species are the subject of scientific interest in the area of multicellular organism MORPHOGENESIS.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Trypsin Inhibitors: Serine proteinase inhibitors which inhibit trypsin. They may be endogenous or exogenous compounds.Solanum tuberosum: A plant species of the genus SOLANUM, family SOLANACEAE. The starchy roots are used as food. SOLANINE is found in green parts.Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).Powders: Substances made up of an aggregation of small particles, as that obtained by grinding or trituration of a solid drug. In pharmacy it is a form in which substances are administered. (From Dorland, 28th ed)Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).Antibody Specificity: The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Antibodies, Viral: Immunoglobulins produced in response to VIRAL ANTIGENS.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Antibodies, Bacterial: Immunoglobulins produced in a response to BACTERIAL ANTIGENS.Disease-Free Survival: Period after successful treatment in which there is no appearance of the symptoms or effects of the disease.Antibody Formation: The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.Antibodies, Neutralizing: Antibodies that reduce or abolish some biological activity of a soluble antigen or infectious agent, usually a virus.Intermediate Filament Proteins: Filaments 7-11 nm in diameter found in the cytoplasm of all cells. Many specific proteins belong to this group, e.g., desmin, vimentin, prekeratin, decamin, skeletin, neurofilin, neurofilament protein, and glial fibrillary acid protein.Keratins: A class of fibrous proteins or scleroproteins that represents the principal constituent of EPIDERMIS; HAIR; NAILS; horny tissues, and the organic matrix of tooth ENAMEL. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms a coiled-coil alpha helical structure consisting of TYPE I KERATIN and a TYPE II KERATIN, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. alpha-Keratins have been classified into at least 20 subtypes. In addition multiple isoforms of subtypes have been found which may be due to GENE DUPLICATION.Cornified Envelope Proline-Rich Proteins: A family of low molcular-weight proteins that contain PROLINE-RICH PROTEIN DOMAINS. Members of this family play a role in the formation of an insoluble cornified envelope beneath the plasma membrane of stratified squamous epithelial cells.Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell.Epidermis: The external, nonvascular layer of the skin. It is made up, from within outward, of five layers of EPITHELIUM: (1) basal layer (stratum basale epidermidis); (2) spinous layer (stratum spinosum epidermidis); (3) granular layer (stratum granulosum epidermidis); (4) clear layer (stratum lucidum epidermidis); and (5) horny layer (stratum corneum epidermidis).Caspase 14: A short pro-domain caspase that is almost exclusively expressed in the EPIDERMIS and may play a role in the differentiation of epidermal KERATINOCYTES.Pick Disease of the Brain: A rare form of DEMENTIA that is sometimes familial. Clinical features include APHASIA; APRAXIA; CONFUSION; ANOMIA; memory loss; and personality deterioration. This pattern is consistent with the pathologic findings of circumscribed atrophy of the poles of the FRONTAL LOBE and TEMPORAL LOBE. Neuronal loss is maximal in the HIPPOCAMPUS, entorhinal cortex, and AMYGDALA. Some ballooned cortical neurons contain argentophylic (Pick) bodies. (From Brain Pathol 1998 Apr;8(2):339-54; Adams et al., Principles of Neurology, 6th ed, pp1057-9)Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory.Editorial Policies: The guidelines and policy statements set forth by the editor(s) or editorial board of a publication.Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.Amyloid beta-Protein Precursor: A single-pass type I membrane protein. It is cleaved by AMYLOID PRECURSOR PROTEIN SECRETASES to produce peptides of varying amino acid lengths. A 39-42 amino acid peptide, AMYLOID BETA-PEPTIDES is a principal component of the extracellular amyloid in SENILE PLAQUES.Postmortem Changes: Physiological changes that occur in bodies after death.

Cyclin D1 proteolysis: a retinoid chemoprevention signal in normal, immortalized, and transformed human bronchial epithelial cells. (1/2088)

BACKGROUND: Retinoids (derivatives of vitamin A) are reported to reduce the occurrence of some second primary cancers, including aerodigestive tract tumors. In contrast, beta-carotene does not reduce the occurrence of primary aerodigestive tract cancers. Mechanisms explaining these effective retinoid and ineffective carotenoid chemoprevention results are poorly defined. Recently, the all-trans-retinoic acid (RA)-induced proteolysis of cyclin D1 that leads to the arrest of cells in G1 phase of the cell cycle was described in human bronchial epithelial cells and is a promising candidate for such a mechanism. In this study, we have investigated this proteolysis as a common signal used by carotenoids or receptor-selective and receptor-nonselective retinoids. METHODS: We treated cultured normal human bronchial epithelial cells, immortalized human bronchial epithelial cells (BEAS-2B), and transformed human bronchial epithelial cells (BEAS-2BNNK) with receptor-selective or receptor-nonselective retinoids or with carotenoids and studied the effects on cell proliferation by means of tritiated thymidine incorporation and on cyclin D1 expression by means of immunoblot analysis. We also examined whether calpain inhibitor I, an inhibitor of the 26S proteasome degradation pathway, affected the decline (i.e., proteolysis) of cyclin D1. RESULTS: Receptor-nonselective retinoids were superior to the carotenoids studied in mediating the decline in cyclin D1 expression and in suppressing the growth of bronchial epithelial cells. Retinoids that activated retinoic acid receptor beta or retinoid X receptor pathways preferentially led to a decrease in the amount of cyclin D1 protein and a corresponding decline in growth. The retinoid-mediated degradation of cyclin D1 was blocked by cotreatment with calpain inhibitor I. CONCLUSIONS: Retinoid-dependent cyclin D1 proteolysis is a common chemoprevention signal in normal and neoplastic human bronchial epithelial cells. In contrast, carotenoids did not affect cyclin D1 expression. Thus, the degradation of cyclin D1 is a candidate intermediate marker for effective retinoid-mediated cancer chemoprevention in the aerodigestive tract.  (+info)

Modifications to rat lens major intrinsic protein in selenite-induced cataract. (2/2088)

PURPOSE: To identify modifications to rat lens major intrinsic protein (MIP) isolated from selenite-induced cataract and to determine whether m-calpain (EC 3.4.22.17) is responsible for cleavage of MIP during cataractogenesis. METHODS: Cataracts were induced in rats by a single injection of sodium selenite. Control and cataract lenses were harvested on day 16 and dissected into cortical and nuclear regions. Membranes were washed with urea buffer followed by NaOH. The protein was reduced/alkylated, delipidated, and cleaved with cyanogen bromide (CNBr). Cleavage products were fractionated by high-performance liquid chromatography (HPLC), and peptides were characterized by mass spectrometry and tandem mass spectrometry. MIP cleavage by m-calpain was carried out by incubation with purified enzyme, and peptides released from the membrane were analyzed by Edman sequencing. RESULTS: The intact C terminus, observed in the control nuclear and cataractous cortical membranes, was not observed in the cataractous nuclear membranes. Mass spectrometric analysis revealed heterogeneous cleavage of the C terminus of MIP in control and cataract nuclear regions. The major site of cleavage was between residues 238 and 239, corresponding to the major site of in vitro cleavage by m-calpain. However, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and mass spectrometric analysis indicated that in vivo proteolysis during cataract formation also included sites closer to the C terminus not produced by m-calpain in vitro. Evidence for heterogeneous N-terminal cleavage was also observed at low levels with no differences between control and cataractous lenses. The major site of phosphorylation was determined to be at serine 235. CONCLUSIONS: Specific sites of MIP N- and C-terminal cleavage in selenite-induced cataractous lenses were identified. The heterogeneous cleavage pattern observed suggests that m-calpain is not the sole enzyme involved in MIP C-terminal processing in rat lens nuclei.  (+info)

Caspase-dependent activation of calpain during drug-induced apoptosis. (3/2088)

We have previously demonstrated that calpain is responsible for the cleavage of Bax, a proapoptotic protein, during drug-induced apoptosis of HL-60 cells (Wood, D. E., Thomas, A., Devi, L. A., Berman, Y., Beavis, R. C., Reed, J. C., and Newcomb, E. W. (1998) Oncogene 17, 1069-1078). Here we show the sequential activation of caspases and calpain during drug-induced apoptosis of HL-60 cells. Time course experiments using the topoisomerase I inhibitor 9-amino-20(S)-camptothecin revealed that cleavage of caspase-3 substrates poly(ADP-ribose) polymerase (PARP) and the retinoblastoma protein as well as DNA fragmentation occurred several hours before calpain activation and Bax cleavage. Pretreatment with the calpain inhibitor calpeptin blocked calpain activation and Bax cleavage but did not inhibit PARP cleavage, DNA fragmentation, or 9-amino-20(S)-camptothecin-induced morphological changes and cell death. Pretreatment with the pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-fmk) inhibited PARP cleavage, DNA fragmentation, calpain activation, and Bax cleavage and increased cell survival by 40%. Interestingly, Z-VAD-fmk-treated cells died in a caspase- and calpain-independent manner that appeared morphologically distinct from apoptosis. Our results suggest that excessive or uncontrolled calpain activity may play a role downstream of and distinct from caspases in the degradation phase of apoptosis.  (+info)

Degradation of protein kinase Malpha by mu-calpain in a mu-calpain-protein kinase Calpha complex. (4/2088)

In previous studies, we isolated and identified a mu-calpain-PKCalpha complex from rabbit skeletal muscle. At the same time we pointed out that an association between mu-calpain and PKCalpha could occur at the level of the plasma membrane of muscle cells, and that PKCalpha could thus be considered as a potential mu-calpain substrate. In the present study, using the mu-calpain-PKCalpha complex as a model, we report that mu-calpain is activated in the combined presence of physiological calcium concentrations (less than 1 microM) and phosphatidylserine. Furthermore our data also show that: (1) there exists a correlation between the appearance of autolyzed mu-calpain forms and PKCalpha hydrolysis which leads to the formation of PKMalpha; (2) in certain experimental conditions, autolyzed mu-calpain forms are able to hydrolyze PKMalpha independently of the presence of diacylglycerol.  (+info)

Hydrostatic pressure and calcium-induced dissociation of calpains. (5/2088)

The dissociation of mu- and m-calpains was studied by fluorescence spectroscopy under high hydrostatic pressure (up to 650 MPa). Increasing pressure induced a red shift of the tryptophan fluorescence of the calcium-free enzyme. The concentration dependence of the spectral transition was consistent with a pressure-induced dissociation of the subunits. Rising temperature increased the stability of calpain heterodimers and confirmed the predominance of hydrophobic interactions between monomers. At saturating calcium, the spectral transition was not observed for native or iodoacetamide-inactivated calpains, indicating that they were already dissociated by calcium. The reaction volume was about -150 ml mol-1 for both isoforms, and the dissociation constants at atmospheric pressure are approximately 10-12 M and 10-15 M for mu- and m-calpains, respectively. This result indicates a tighter interaction in the isoform that requires higher calcium concentration for activity.  (+info)

Calpain inhibitor I increases beta-amyloid peptide production by inhibiting the degradation of the substrate of gamma-secretase. Evidence that substrate availability limits beta-amyloid peptide production. (6/2088)

The calpain inhibitor N-acetyl-leucyl-leucyl-norleucinal (ALLN) has been reported to have complex effects on the production of the beta-amyloid peptide (Abeta). In this study, the effects of ALLN on the processing of the amyloid precursor protein (APP) to Abeta were examined in 293 cells expressing APP or the C-terminal 100 amino acids of APP (C100). In cells expressing APP or low levels of C100, ALLN increased Abeta40 and Abeta42 secretion at low concentrations, decreased Abeta40 and Abeta42 secretion at high concentrations, and increased cellular levels of C100 in a concentration-dependent manner by inhibiting C100 degradation. Low concentrations of ALLN increased Abeta42 secretion more dramatically than Abeta40 secretion. ALLN treatment of cells expressing high levels of C100 did not alter cellular C100 levels and inhibited Abeta40 and Abeta42 secretion with similar IC50 values. These results suggest that C100 can be processed both by gamma-secretase and by a degradation pathway that is inhibited by low concentrations of ALLN. The data are consistent with inhibition of gamma-secretase by high concentrations of ALLN but do not support previous assertions that ALLN is a selective inhibitor of the gamma-secretase producing Abeta40. Rather, Abeta42 secretion may be more dependent on C100 substrate concentration than Abeta40 secretion.  (+info)

Posttranslational regulation of the retinoblastoma gene family member p107 by calpain protease. (7/2088)

The retinoblastoma protein plays a critical role in regulating the G1/S transition. Less is known about the function and regulation of the homologous pocket protein p107. Here we present evidence for the posttranslational regulation of p107 by the Ca2+-activated protease calpain. Three negative growth regulators, the HMG-CoA reductase inhibitor lovastatin, the antimetabolite 5-fluorouracil, and the cyclic nucleotide dibutyryl cAMP were found to induce cell type-specific loss of p107 protein which was reversible by the calpain inhibitor leucyl-leucyl-norleucinal but not by the serine protease inhibitor phenylmethylsulfonylfluoride, caspase inhibitors, or lactacystin, a specific inhibitor of the 26S proteasome. Purified calpain induced Ca2+-dependent p107 degradation in cell lysates. Transient expression of the specific calpain inhibitor calpastatin blocked the loss of p107 protein in lovastatin-treated cells, and the half-life of p107 was markedly lengthened in lovastatian-treated cells stably transfected with a calpastatin expression vector versus cells transfected with vector alone. The data presented here demonstrate down-regulation of p107 protein in response to various antiproliferative signals, and implicate calpain in p107 posttranslational regulation.  (+info)

Ubiquitination and degradation of ATF2 are dimerization dependent. (8/2088)

Ubiquitination and proteasome-dependent degradation are key determinants of the half-lives of many transcription factors. Homo- or heterodimerization of basic region-leucine zipper (bZIP) transcription factors is required for their transcriptional activities. Here we show that activating transcription factor 2 (ATF2) heterodimerization with specific bZIP proteins is an important determinant of the ubiquitination and proteasome-dependent degradation of ATF2. Depletion of c-Jun as one of the ATF2 heterodimer partners from the targeting proteins decreased the efficiency of ATF2 ubiquitination in vitro, whereas the addition of exogenously purified c-Jun restored it. Similarly, overexpression of c-Jun in 293T human embryo kidney cells increased ATF2 ubiquitination in vivo and reduced its half-life in a dose-dependent manner. Mutations of ATF2 that disrupt its dimerization inhibited ATF2 ubiquitination in vitro and in vivo. Conversely, removal of residues 150 to 248, as in a constitutively active ATF2 spliced form, enhanced ATF2 dimerization and transactivation, which coincided with increased ubiquitination and decreased stability. Our findings indicate the increased sensitivity of transcriptionally active dimers of ATF2 to ubiquitination and proteasome-dependent degradation. Based on these observations, we conclude that increased targeting of a transcriptionally active ATF2 form indicates the mechanism by which the magnitude and the duration of the cellular stress response are regulated.  (+info)

A calpain (/ˈkælpeɪn/; EC 3.4.22.52, EC 3.4.22.53) is a protein belonging to the family of calcium-dependent, non-lysosomal cysteine proteases (proteolytic enzymes) expressed ubiquitously in mammals and many other organisms. Calpains constitute the C2 family of protease clan CA in the MEROPS database. The calpain proteolytic system includes the calpain proteases, the small regulatory subunit CAPNS1, also known as CAPN4, and the endogenous calpain-specific inhibitor, calpastatin. The history of calpain originates in 1964, when calcium-dependent proteolytic activities caused by a "calcium-activated neutral protease" (CANP) were detected in brain, lens of the eye and other tissues. In the late 1960s the enzymes were isolated and characterised independently in both rat brain and skeletal muscle. These activities were caused by an intracellular cysteine protease not associated with the lysosome and having an optimum activity at neutral pH, which clearly distinguished it from the cathepsin family ...
Calpastatin (CAST) is a calpain inhibitor, a calcium-dependent cysteine protease that is widely distributed in higher order animals. There are different types of calpastatins; examples include the 68 kDa erythrocyte-derived calpastatin and the 107 kDa myocyte-derived calpastatin (as evidenced by SDS-PAGE). Through its inhibition of calpain, calpastatin is believed to play important roles in the regulation of cell proliferation, differentiation and aging. CAST is also involved in the proteolysis of amyloid precursor protein (APP). ...
Calpastatin (CAST) is a calpain inhibitor, a calcium-dependent cysteine protease that is widely distributed in higher order animals. There are different types of calpastatins; examples include the 68 kDa erythrocyte-derived calpastatin and the 107 kDa myocyte-derived calpastatin (as evidenced by SDS-PAGE). Through its inhibition of calpain, calpastatin is believed to play important roles in the regulation of cell proliferation, differentiation and aging. CAST is also involved in the proteolysis of amyloid precursor protein (APP). ...
Calpains are calcium-dependent cysteine proteases involved in signal transduction in a variety of cellular processes. A functional calpain protein consists of an invariant small subunit and 1 of a family of large subunits. CAPN5 is one of the large subunits. Unlike some of the calpains, CAPN5 and CAPN6 lack a calmodulin-like domain IV. Because of the significant similarity to Caenorhabditis elegans sex determination gene tra-3, CAPN5 is also called as HTRA3. [provided by RefSeq, Jul 2008 ...
Calpain II was purified to apparent homogeneity from bovine neural retinas. It was found to be biochemically similar to brain calpain II, purified by the same procedure, with respect to: subunit mobility in SDS-polyacrylamide gel electrophoresis; Ca2+ sensitivity; inhibition by calpeptin and other cysteine protease inhibitors; and optimal pH. Semithin cryosections were immuno-labeled with antibodies specific for the catalytic subunit of calpain II. Calpain II was detected in most layers of the retina, with the most pronounced label present in the plexiform layers (synaptic regions) and the photoreceptor outer segments. In dark-adapted retinas, the label was distributed throughout the outer segments. In light-adapted retinas, outer segment labeling was concentrated in the connecting cilium, and the inner segments were labeled. A partially pure preparation of calpain II from isolated rod outer segments was found to have the same biochemical characteristics as calpain II prepared in the same way ...
Cell-attached and whole-cell patch-clamp recordings were done at 32°C from visually identified CA1 pyramidal neurons using an EPC 10 amplifier and Pulse software (HEKA). Patch pipettes were fabricated from borosilicate glass (Harvard Apparatus), and their resistance ranged from 4.5 to 6.5 MΩ. The pipette solution consisted of (in mm): 30 N-methyl-d-glucamine-HCl, 95 K-gluconate, 1 EGTA, 5 HEPES, 10 d-glucose, 2 Mg-ATP, 20 sucrose, 0.1 Alexa Fluor 488, 2 NaOH, and 5.4 KOH, pH 7.3. For recordings, slices were positioned in a submerged-type recording chamber and continuously perfused at a rate of 3.5 ml/min with extracellular solution containing (in mm): 124 NaCl, 3.5 KCl, 2 CaCl2, 25 NaHCO3, 1.1 NaH2PO4, 2 MgSO4, and 10 d-glucose, equilibrated with 95% O2 and 5% CO2, pH 7.4. Membrane potential values were corrected for calculated liquid junction potentials (Barry, 1994). Interictal-like activity was induced by omitting Mg2+ from the extracellular solution after recovery and during the recordings ...
The c-Fos and c-Jun transcription factors are rapidly turned over in vivo. One of the multiple pathways responsible for their breakdown is probably initiated by calpains, which are cytoplasmic calcium-dependent cysteine proteases. The c-fos gene has been transduced by two murine oncogenic retroviruses called Finkel-Biskis-Jenkins murine sarcoma virus (FBJ-MSV) and Finkel-Biskis-Reilly murine sarcoma virus (FBR-MSV); c-jun has been transduced by the chicken avian sarcoma virus 17 (ASV17) retrovirus. Using an in vitro degradation assay, we show that the mutated v-FosFBR, but not v-FosFBJ or v-JunASV17, is resistant to calpains. This property raises the interesting possibility that decreased sensitivity to calpains might contribute to the tumorigenic potential of FBR-MSV by allowing greater accumulation of the protein that it encodes in infected cells. It has also been demonstrated that resistance to cleavage by calpains does not result from mutations that have accumulated in the Fos moiety of the ...
Calpains are calcium-dependent cysteine proteases involved in sigl transduction in a variety of cellular processes. A functiol calpain protein…
Calpains make up a ubiquitously expressed, well-conserved family of calcium-dependent cysteine proteases. The calpain proteins are heterodimers…
The major finding of the present study is that type 2 diabetes mellitus is associated with the cleavage of platelet PECAM-1 through a mechanism involving the tyrosine nitration of SERCA-2, an increase in [Ca2+]i, and the activation of the Ca2+-dependent protease μ-calpain. Moreover, treating subjects with type 2 diabetes mellitus with the PPAR-γ agonist rosiglitazone successfully reversed many of these changes and restored platelet [Ca2+]i, calpain activity, and PECAM-1 to levels comparable to those detected in nondiabetic subjects. From these results, it is clear that megakaryocytes/platelets are an additional cellular target for PPAR-γ agonists.. Intracellular Ca2+ homeostasis in platelets from patients with type 2 diabetes mellitus is reported to be altered, leading to an increased adhesiveness and spontaneous aggregation. One factor that contributes to the disturbed platelet [Ca2+]i in diabetic subjects is a marked reduction in Ca2+-ATPase activity.3,4 Although human platelets coexpress ...
The report generally describes calpain inhibitor i, examines its uses, production methods, patterns. CALPAIN INHIBITOR I market situation is overviewed;
Oxidized low-density lipoprotein (oxLDL) is known to induce apoptosis in endothelial cells, and this is believed to contribute to the progression of atherosclerosis. In the present study we made the novel observation that oxLDL-induced death of HMEC-1 cells is accompanied by activation of calpain. The μ-calpain inhibitor PD 151746 decreased oxLDL-induced cytotoxicity, whereas the general caspase inhibitor BAF (t-butoxycarbonyl-Asp-methoxyfluoromethylketone) had no effect. Also, oxLDL provoked calpain-dependent proteolysis of cytoskeletal α-fodrin in the HMEC-1 cells. Our observation of an autoproteolytic cleavage of the 80 kDa subunit of μ-calpain provided further evidence for an oxLDL-induced stimulation of calpain activity. The Bcl-2 protein Bid was also cleaved during oxLDL-elicited cell death, and this was prevented by calpain inhibitors, but not by inhibitors of cathepsin B and caspases. Treating the HMEC-1 cells with oxLDL did not result in detectable activation of procaspase 3 or ...
Comparative Studies on Metabolic Rate and Calpain/Calpastatin Activity between Hanwoo and Holstein Beef - Hanwoo Beef;Holstein Beef;Temperature Conditioning;Metabolic Rate;Calpain;Calpastatin;
To The Editor:. In the March 28, 2008 issue of Circulation Research, Letavernier et al assessed the effects of calpain inhibition on angiotensin (Ang) II-induced cardiovascular remodeling.1 These authors used transgenic mice expressing high levels of calpastatin to inhibit Ang II-dependent calpain activation. They show that prevention of Ang II-induced calpain activation is associated with impaired nuclear factor (NF)-κB activation in heart tissue, which eventually leads to decreased Ang II-induced cardiac hypertrophy. This finding adds substantial novel information to our understanding of how calpains might be involved in the complex regulation of cardiac hypertrophy. However, compelling evidence as to how calpains are activated by Ang II in the myocardium and how the calpain/calpastatin system is linked to NF-κB activation is not provided. In the May 23, 2008 issue of Circulation Research, we show that Ang II induces calcium release via the inositol 1,4,5-trisphosphate receptor (InsP3R) ...
Ionotropic glutamate receptors mediate most excitatory synaptic transmission in mammalian brain, and play important roles in neuronal development and synaptic plasticity. In particular, long-term potentiation (LTP) and long-term depression (LTD) are generally considered to represent cellular mechanisms involved in certain forms of learning and memory. Calpain is a calcium-dependent neutral protease that plays significant roles in synaptic plasticity, cell motility, as well as in various forms of neurodegeneration. We compared the rates of calpain-mediated truncation of GluR1 and GluR2 subunits with those of GluR1 phosphorylated at serine 831 or serine 845, and GluR2 phosphorylated at serine 880. Rat brain membranes were treated with calpain and calcium and levels of total and phosphorylated GluR1 and GluR2 subunits were analyzed by western blots. Rates of calpain-mediated truncation of phosphorylated GluR1 (either at serine 831 or 845) were much slower than for total GluR1. On the other hand, ...
Results Doxorubicin decreased calpain activities in cultured neonatal mouse cardiomyocytes and in vivomouse hearts, which correlated with down-regulation of calpain-1 and calpain-2 proteins. Over-expression of calpastatin or treatment with pharmacological calpain inhibitors aggravated apoptosis in neonatal and adult cardiomyocytes caused by doxorubicin. On the while, over-expression of calpain-2 but not calpain-1 decreased doxorubicin-induced apoptosis in cardiomyocytes. The pro-apoptotic effects of calpain inhibition were concerned with down-regulation of AKT protein and mRNA expression, and a concomitant reduction in GSK-3 beta phosphorylation (Ser9) in doxorubicin-treated cardiomyocytes. Inhibiting AKT further increased doxorubicin-induced cardiac injuries, suggesting the effects of calpain inhibition may be mediated through inactivating the AKT signalling. In an in vivomodel of doxorubicin-induced cardiotoxicity, overexpression of calpastatin aggravated myocardial dysfunction in transgenic ...
Abstract: : Purpose: Our previous study suggested that calpains played an important role in retinal cell death induced by ischemia-reperfusion in rat. However, the relationship between changes in signaling pathways caused by activation of calpain and retinal cell death is not clear. Recently, calpain-induced proteolysis of p35, a regulator of cdk5, to p25 was reported in Alzheimers disease. Thus, the purpose of present study to determine if p35 was similarly proteolyzed by m-calpain to p25 during retinal cell damage occurring in vitro. Methods: Rat retinas were incubated in RPMI medium with glucose under conditions supplying oxygen sufficient for retinal cell survival. To induce a hypoxia, retinas were incubated in RPMI medium without glucose under 95 % N2/5 % CO2 instead of 95 % O2/5 % CO2. Leakage of LDH into the medium assessed membrane damage and cell death. Casein zymography and immunoblotting assessed activation of calpain and proteolysis of α-spectrin and p35. Results: Results Leakage ...
TY - JOUR. T1 - CAPN5 mutation in hereditary uveitis. T2 - The R243L mutation increases calpain catalytic activity and triggers intraocular inflammation in a mouse model. AU - Wert, Katherine J.. AU - Bassuk, Alexander G.. AU - Wu, Wen Hsuan. AU - Gakhar, Lokesh. AU - Coglan, Diana. AU - Mahajan, Mary Ann. AU - Wu, Shu. AU - Yang, Jing. AU - Lin, Chyuan Sheng. AU - Tsang, Stephen H.. AU - Mahajan, Vinit B.. PY - 2015/4/28. Y1 - 2015/4/28. N2 - A single amino acid mutation near the active site of the CAPN5 protease was linked to the inherited blinding disorder, autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV, OMIM #193235). In homology modeling with other calpains, this R243L CAPN5 mutation was situated in a mobile loop that gates substrate access to the calcium-regulated active site. In in vitro activity assays, the mutation increased calpain protease activity and made it far more active at low concentrations of calcium. To test whether the disease allele could yield an ...
Gentaur molecular products has all kinds of products like :search , Biovis \ Calpain Inhibitor I, ALLN; Appearance White powder \ 1834-25 for more molecular products just contact us
Two types of cell death can be distinguished by morphological features, although it is likely that these are two ends of a spectrum with possible intermediate forms. Apoptosis involves shrinkage, nuclear disassembly, and fragmentation of the cell into discrete bodies with intact plasma membranes. These are rapidly phagocytosed by neighbouring cells. An important feature of apoptosis is the requirement for adenosine triphosphate (ATP) to initiate the execution phase. In contrast, necrotic cell death is characterized by cell swelling and lysis. This is usually a consequence of profound loss of mitochondrial function and resultant ATP depletion, leading to loss of ion homeostasis, including volume regulation, and increased Ca2+. The latter activates a number of nonspecific hydrolases (i.e., proteases, nucleases, and phospholipases) as well as calcium dependent kinases. Activation of calpain I, the Ca2+-dependent cysteine protease cleaves the death-promoting Bcl-2 family members Bid and Bax which ...
Calpain-like mRNAs have been identified in other organisms including bacteria, but the molecules encoded by these mRNAs have not been isolated, so little is known about their properties. How calpain activity is regulated in these organisms cells is still unclear In metazoans, the activity of calpain is controlled by a single proteinase inhibitor, calpastatin (IPR001259). The calpastatin gene can produce eight or more calpastatin polypeptides ranging from 17 to 85 kDa by use of different promoters and alternative splicing events. The physiological significance of these different calpastatins is unclear, although all bind to three different places on the calpain molecule; binding to at least two of the sites is Ca2+ dependent. The calpains ostensibly participate in a variety of cellular processes including remodelling of cytoskeletal/membrane attachments, different signal transduction pathways, and apoptosis. Deregulated calpain activity following loss of Ca2+ homeostasis results in tissue damage ...
Fulvestrant (ICI 182 780, ICI) has been used in treating patients with hormone-sensitive breast cancer, yet initial or acquired resistance to endocrine therapies frequently arises and, in particular, cancer recurs as metastasis. We demonstrate here that both 17-beta-estradiol (E2) and ICI enhance cell adhesion to matrigel in MCF-7 breast cancer cells, with increased autolysis of calpain 1 (large subunit) and proteolysis of focal adhesion kinase (FAK), indicating calpain activation. Additionally, either E2 or ICI induced down-regulation of estrogen receptor α without affecting G protein coupled estrogen receptor 30 (GPR30) expression. Interestingly, GPR30 agonist G1 triggered calpain 1 autolysis but not calpain 2, whereas ER agonist diethylstilbestrol caused no apparent calpain autolysis. Furthermore, the actions of E2 and ICI on calpain and cell adhesion were tremendously suppressed by G15, or knockdown of GPR30. E2 and ICI also induced phosphorylation of extracellular regulated protein kinases ...
Hypoxia-specific upregulation of calpain activity and gene expression in pulmonary artery endothelial cells.: The effects of exposure to hypoxia on the catalyti
Methods Male wild type mice were randomly divided into control and PD150606 groups. Mice were subjected to myocardial ischemia by occlusion of the left anterior descending coronary artery for 45 min and reperfusion for 3 h (I/R). Terminal deoxynucleotidyl transferase d-UTP nick end labeling (TUNEL) staining was performed using an In Situ Cell Death Detection kit on paraffin heart sections (5 mm). Hoechst 33342 was used as a counter-stain. Adult mouse cardiomyocytes were isolated and cultured, then subjected to ischemia for 1 h, and reperfusion for 3 h. The survival of cardiomyocytes, activity of calpain and caspase-3, cytoplasmic DNA fragments and cytochrome c concentrations were determined. Results Compared to control, the numbers of TUNEL-positive nuclei were significantly increased in the peri-infarct area in I/R mice (p,0.05). Compared to normal cultured cardiomyocytes, the survival of the cells significantly decreased, however the activation of calpain and caspase-3, and cytoplasmic DNA ...
The pSUPER.retro (Oligoengine) RNA interference system was used to achieve stable expression of siRNAs. Oligonucleotides targeted to calpain 2 or PTP1B mRNA as well as a nonsilencing control were synthesized by Integrated DNA Technologies, annealed, and cloned into the pSUPER.retro.puro vector according to manufacturers instructions. Retroviral transfection was performed as described previously (Franco et al., 2004a). Wild-type MTLn3 cells were infected at 32°C for 6 h and allowed to recover in growth medium for 24 h before selection with 1 μg/ml puromycin for 4-5 d. Target sequences for calpain 2 in MTLn3 cells: control, 5′-TTCTCCGAACGTGTCACGT-3′; Capn2 si-A, 5′-AGGCCTATGCCAAGATCAA-3′; and Capn2 si-B, 5′-GAATGGCGATTTCTGCATC-3′. Target sequences for PTP1B in MTLn3 cells: PTP1B si-A, 5′-GCTGACACTGATCTCTGAA-3′; and PTP1Bsi-B, 5′-CAGGAGGAGCCTTGGTGTC-3′. Target sequences for human calpain 2 have been described previously (Su et al., 2006). Target sequences for cortactin: ...
Health, ...EDITORS PICK: Calpain inhibitors never forget: improving memory in Al...Overactivation of proteins known as calpains which are involved in me...It is thought that dysfunctional signaling between nerve cells contrib...TITLE: Inhibition of calpains improves memory and synaptic transmissio...,JCI,online,early,table,of,contents:,July,1,,2008,medicine,medical news today,latest medical news,medical newsletters,current medical news,latest medicine news
Calpains encompass a family of calcium-dependent, nonlysosomal proteases characterized by a cysteine-protease domain that includes a conserved catalytic sequence Cys-His-Arg combined with a calmodulin-like Ca2+-binding site (Sorimachi and Suzuki 2001). The configuration of the cysteine-protease domain determines the formation of an active catalytic pocket, which only occurs when calcium is present. Calpains are involved in a large variety of calcium-regulated processes, such as signal transduction, cell proliferation, and PCD (Goll et al. 2003).. The calpain family comprises a heterogeneous group of cysteine proteases with a large expression pattern. The proteases belonging to this family have been subdivided into three groups depending on their primary structure and the presence or absence of regulatory subunits. These three groups are defined as: typical (also called ubiquitous or conventional), atypical, and other EF-calpains (Goll et al. 2003; Saez et al. 2006). The most important and most ...
Calpain represents a family of Ca(2+)-dependent cytosolic cysteine proteases found in almost all eukaryotes and some bacteria, and is involved in a variety of biological phenomena, including brain function. Several substrates of calpain are aggressively proteolyzed under pathological conditions, e.g …
Gentaur molecular products has all kinds of products like :search , Biovis \ Calpain Inhibitor Z-LLY-FMK \ 1125-20C for more molecular products just contact us
Sigma-Aldrich offers Sigma-A6060, Calpain Inhibitor II for your research needs. Find product specific information including CAS, MSDS, protocols and references.
Calpains are a family of intracellular cysteine proteases activated by calcium. They participate in many processes including cell motility, cell cycle progression and cell death, in response to calcium signaling. Because ...
M2 Ethyl methanesulfonate (EMS) mutagenized Ler seeds were purchased from Lehle Seeds and examined under a dissecting microscope for the absence of giant cells in the sepal.. The dek1-4 mutation isolated contains a C to T change at base 6316 of the CDS, which causes a single amino acid substitution of a cysteine for conserved arginine 2106 in domain III of the calpain protease (supplementary material Fig. S2A) (Sorimachi and Suzuki, 2001). The dek1-4 allele fails to complement the reference dek1-3 (SAIL_384_G07) allele (data not shown), establishing that the absence of giant cells is due to the mutation in the DEK1 gene.. The dek1-4 mutation can be PCR genotyped by amplifying with oAR448 (5′-TGTTGGTGGAACAGACTATGTGAATTCA-3′) and oAR449 (5′-TGAAGACTGAAAGGACAAAAGGTGC-3′) with a 60°C annealing temperature followed by digesting the product with BsaAI to produce a 108 bp wild-type product or a 137 bp mutant product.. The atml1-2 allele isolated in this mutant screen contains a C to T change ...
Despite great advances in our knowledge of calpains 1 and 2, much is yet to be learned about the evolution of the family and the range of functions of its members. Genomic sequences from a wide range of organisms document the extreme diversity and modular nature of the calpain protein family. Current evidence suggests that the acquisition of the penta-EF-hand module, characteristic of the classical calpains, may be restricted to animals, but that EF-hands may have been acquired independently in Tetrahymena calpains. The use of different strategies for associating with membranes, such as transmembrane domains, C2-like domains, and acylation, support the importance of membrane association in calpain function. More genomic information from representative organisms, particularly protozoa, is required to better analyze the evolutionary relationships within this family. The proteolytic core module is now relatively well characterized as to structure and function. Distinguishing the overlapping or ...
4PHK: The Structural Basis of Differential Inhibition of Human Calpain by Indole and Phenyl alpha-Mercaptoacrylic Acids. The complex with (Z)-3-(4-chlorophenyl)-2-mercaptoacrylic acid
Calpain兔多克隆抗体(ab124631)可与小鼠, 大鼠, 人, 曼氏血吸虫样本反应并经WB, IP, ELISA实验严格验证。所有产品均提供质保服务,中国75%以上现货。
Welcome! For price inquiries, please feel free to contact us through the form below through the form on the left side. We will get back to you as soon as possible.. ...
Zheng, T. , Rakic, P. and Flavell, R A. Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice. Nature 1996, 384, 368-72. , Soengas, M. , Duncan, G. , Kaufman, S. , Lowe, S. W. and Mak, T. W. Essential contribution of caspase-3/CPP32 to apoptosis and its associated nuclear changes. Genes Dev 1998, 12, 806-19. , Braun, M. , Denis, F. and Sekaly, R. P. Specific activation of the cysteine protease CPP32 during the negative selection of T cells in the thymus. J Exp Med 1997, 186, 1503-12. The route leading from ER stress to caspase-12 activation, however, remains unclear. There is evidence, however, suggesting that release of intracellular calcium stores associated with ER stress activates the protease calpain, which in turn can activate caspase-12 and lead to apoptosis [105]. 10 Compensatory Caspase Activation: A Caveat to Knockout Analysis Although the generation of knockout animals has vastly increased our knowledge of the cellular apoptotic machinery, one difficulty in ...
A family of calcium-dependent proteolytic enzymes, that are classified as non-lysosomal cysteine proteases. The enzyme can selectively cleave proteins in response to signaling (calcium signals) thought to be involved in cytoskeletal changes, cell cycle, gene expression and apoptotic cell death. Calpain 1 (micro-calpain) and 2 (m-calpain), are ubiquitously expressed and their activity is inhibited by calpastatin. PMID: 12843408 ...
Calpain 2 antibody [N2C1], Internal (calpain 2, (m/II) large subunit) for FACS, ICC/IF, IHC-P, WB. Anti-Calpain 2 pAb (GTX102499) is tested in Human, Mouse samples. 100% Ab-Assurance.
Calpain 5 antibody [N1C1] (calpain 5) for ICC/IF, WB. Anti-Calpain 5 pAb (GTX103264) is tested in Human samples. 100% Ab-Assurance.
Deficiency of Capn4 gene inhibits nuclear factor-κB (NF-κB) protein signaling/inflammation and reduces remodeling after myocardial infarction.: Calpain has been
Complete information for CAPN8 gene (Protein Coding), Calpain 8, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Limaye, P. B., Bhave, V. S., Palkar, P. S., Apte, U. M., Sawant, S. P., Yu, S., Latendresse, J. R., Reddy, J. K. and Mehendale, H. M. (2006), Upregulation of calpastatin in regenerating and developing rat liver: Role in resistance against hepatotoxicity. Hepatology, 44: 379-388. doi: 10.1002/hep.21250 ...
The synthetic peptide used to raise the antibody Cat. No. 200196 is selected from a sequence within the N-term region of Calpain-9. For blocking experiments, a 10 to 100 fold molar excess to antibody is recommended ...
The synthetic peptide used to raise the antibody Cat. No. 200195 is selected from a sequence within the C-term region of Calpain-5. For blocking experiments, a 10 to 100 fold molar excess to antibody is recommended ...
Mouse monoclonal Calpain 2 antibody [1E8] validated for WB, ELISA, ICC/IF and tested in Human and Cow. With 1 independent review.
ウサギ・ポリクローナル抗体 ab28258 交差種: Ms,Rat,Hu 適用: WB,ICC,Flow Cyt,ICC/IF…Calpain 1抗体一覧…画像、プロトコール、文献などWeb上の情報が満載のアブカムの Antibody…
From NCBI Gene:. Calpains represent a ubiquitous, well-conserved family of calcium-dependent cysteine proteases. The calpain proteins are heterodimers consisting of an invariant small subunit and variable large subunits. The large catalytic subunit has four domains: domain I, the N-terminal regulatory domain that is processed upon calpain activation; domain II, the protease domain; domain III, a linker domain of unknown function; and domain IV, the calmodulin-like calcium-binding domain. This gene encodes a large subunit. It is an atypical calpain in that it lacks the calmodulin-like calcium-binding domain and instead has a divergent C-terminal domain. It is similar in organization to calpains 5 and 6. This gene is associated with type 2 or non-insulin-dependent diabetes mellitus (NIDDM), and is located within the NIDDM1 region. Multiple alternative transcript variants have been described for this gene. [provided by RefSeq, Sep 2010]. From UniProt: ...
context: it has been reported that the equilibrium between the erythrocyte protease calpain i and its physiological inhibitor calpastatin is disrupted in patients with essential hypertension. objective: to investigate the activity of non-purified calpain i...
TY - JOUR. T1 - Involvement of calpain in AMPA-induced toxicity to rat cerebellar Purkinje neurons. AU - Mansouri, Bobbak. AU - Henne, William M.. AU - Oomman, Sowmini K.. AU - Bliss, Richard. AU - Attridge, Jennifer. AU - Finckbone, VelvetLee. AU - Zeitouni, Tarek. AU - Hoffman, Trent. AU - Bahr, Ben A.. AU - Strahlendorf, Howard K.. AU - Strahlendorf, Jean C.. PY - 2007/2/28. Y1 - 2007/2/28. N2 - AMPA receptor-elicited excitotoxicity is manifested as both a type of programmed cell death termed dark cell degeneration and edematous necrosis, both of which are linked to increased intracellular Ca2+ concentration. The appearance of marked cytoskeletal changes in response to abusive AMPA receptor activation, coupled with increased intracellular Ca2+ concentration suggests activation of various destructive enzymes such as calpains, a family of Ca2+-dependent cysteine proteases. Since calpains and AMPA have been linked to both necrotic cell death and programmed cell death, we sought to determine the ...
Glioblastoma is an aggressive primary brain tumor with a 5-year survival rate of less than 5%. The ability of glioblastoma cells to invade surrounding brain tissue presents the primary challenge for the success of focal therapeutic approaches. We previously reported that the calcium-activated protease calpain 2 is critical for glioblastoma cell invasion in vitro. Here, we show that expression of calpain 2 is required for the dispersal of glioblastoma cells in a living brain microenvironment. Knockdown of calpain 2 resulted in a 2.9-fold decrease in the invasion of human glioblastoma cells in zebrafish brain. Control cells diffusely migrated up to 450 µm from the site of injection, whereas knockdown cells remained confined in clusters. The invasion study was repeated in organotypic mouse brain tissues, and calpain 2 knockdown cells demonstrated a 2.3-fold lower area of dispersal compared with control cells. In zebrafish brain, glioblastoma cells appeared to migrate in part along the blood ...
ABSTRACT Meat tenderness is one of the most important factors affecting consumers assessment of meat quality. Variation in meat tenderness among chickens is genetically controlled and it is also influenced by environmental factors. There has been an increased interest in genetic polymorphisms associated with the variation in meat tenderness among chicken breeds. Understanding and identifying the polymorphisms of candidate genes will facilitate selection programs for genetic improvement in tenderness. Calpain1 (CAPN1), a gene encoding the enzyme μ-calpain which degrades myofibrillar proteins post-mortem, is a physiological candidate gene for meat tenderness. In Malaysia there are two commercially available chicken lines, native and commercial broilers. Native breeds are known to have lower meat tenderness compared to the broilers. The aim of this study is to investigate the reported association between the single nucleotide polymorphisms (SNPs) G3535A, C7198A and G9950A markers in the CAPN1 ...
Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.. The ability of macrophages to clear pathogens and elicit a sustained immune response is regulated by various cytokines, including interferon-gamma (IFN-gamma). To investigate the molecular mechanisms by which IFN-gamma modulates phagosome functions, we profiled the changes in composition, abundance, and phosphorylation of phagosome proteins in resting and activated macrophages by using quantitative proteomics and bioinformatics approaches. We identified 2415 phagosome proteins together with 2975 unique phosphorylation sites with a high level of sensitivity. Using network analyses, we determined that IFN-gamma delays phagosomal acquisition of lysosomal hydrolases and peptidases for the gain of antigen presentation. Furthermore, this gain in antigen presentation is dependent on phagosomal networks of the actin cytoskeleton and vesicle-trafficking proteins, as well as Src kinases and calpain proteases. Major ...
Apoptosis is a highly conserved process which can be triggered by a broad range of physiological and pathological conditions. Recent evidence suggests that most proapoptotic stimuli induce the activation of a family of intracellular cysteine proteases called caspases ((1), (2)). These proteases are synthesized as inactive proenzymes which, upon proteolytic cleavage at aspartate residues, form an active complex composed of two heterodimeric subunits. Caspases lead to the proteolysis of a number of cellular substrates, a process which finally results in the apoptotic collapse of the cell.. One of the best-defined apoptotic pathways is mediated by the death receptor CD95 (APO-1/Fas; references (3)-(5)). Triggering of CD95 by its natural ligand CD95L or agonistic antibodies induces the formation of a death-inducing signaling complex (DISC) consisting of the adaptor protein Fas-associated death domain protein (FADD [MORT-1]) and procaspase-8 (FADD-like IL-1β-converting enzyme [FLICE, Mch5]) ...
Title: Pharmacological Modulation of Caspase Activation. VOLUME: 4 ISSUE: 4. Author(s):Ute Fischer and Klaus Schulze-Osthoff. Affiliation:Institute of Molecular Medicine, University of Dusseldorf, Building 23.12, Universitatsstr. 1, D-40225Dusseldorf, Germany.. Keywords:apoptosis, caspase, smac, inhibitor, therapy. Abstract: Deregulation of apoptosis resulting either in inappropriate loss or accumulation of cells is a major cause of many severe pathological conditions such as cancer, autoimmune diseases, microbial infections and degenerative disorders. Consequently, great interest has emerged in devising therapeutic strategies for intervening with cell death, either in a pro- or antiapoptotic direction. Among the different apoptosis-based drug targets, caspases, a family of intracellular cysteine proteases are most promising candidates, because they form the central core of the apoptotic machinery that coordinate cell death from various signals. Inappropriate cell death can be efficiently ...
Supplementary Materials Supplemental Materials supp_24_18_2966__index. Dorsal, a take flight NFB/Rel homologue. We display that proteolytic cleavage by CalpA generates Cactus fragments lacking an N-terminal region required for Toll responsiveness. These fragments are generated in vivo and display properties unique from those of full-length Cactus. We propose that CalpA focuses on free Cactus, which is definitely integrated into and modulates Toll-responsive complexes in the embryo and immune system. Intro Calpains are Ca2+-dependent modulatory proteases with several substrates and functions. They have been implicated in several diseases, such as limb-girdle muscular dystrophy, Huntington disease, Alzheimer disease, and malignancy (Bertipaglia and Carafoli, 2007 ). Unlike degrading enzymes, calpains cleave substrates in a limited manner, generating novel activities by substrate proteolysis (Friedrich and Bozoky, 2005 ; Sorimachi to investigate in more detail the mechanism of calpain action and ...
Calpain 3 (CAPN 3) is an intracellular muscle specific nonlysosomal cysteine protease with a variety of cytoskeletal and myofibrillar substrates. CAPN 3 is vital for cytoskeletal rearrangements, sarcomere function, remodeling, and apoptosis (Kramerova et al. 2005). Knockout Capn3 -/- mice do not demonstrate any clinical myopathic signs throughout their lifespan. However on histologic examination progressive myopathy is evident. There are central nuclei present as well as areas of inflammatory infiltrates that increase as the animal ages (Fougerousse et al. 2003). This model was used to elucidate the pathophysiology of LGMD2A.. ...
Background Chronic microglia-mediated inflammation and oxidative stress are well-characterized underlying factors in neurodegenerative disease, whereby reactive inflammatory microglia enhance ROS production and impact neuronal integrity. Recently, it has been shown that during chronic inflammation, neuronal integrity is compromised through targeted disruption of the axon initial segment (AIS), the axonal domain critical for action potential initiation. AIS disruption was associated with contact by reactive inflammatory microglia which wrap around the AIS, increasing association with disease progression. While it is clear that chronic microglial inflammation and enhanced ROS production impact neuronal integrity, little is known about how acute microglial inflammation influences AIS stability. Here, we demonstrate that acute neuroinflammation induces AIS structural plasticity in a ROS-mediated and calpain-dependent manner. Methods C57BL/6J and NOX2−/− mice were given a single injection of
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
Reagents. All chemicals used were commercial products of the highest grade of purity available. The sources of these reagents are detailed in Supplemental Methods.. Mice. Mice were fed chow (CRF-1; Oriental Yeast Co.) or HFD (F2HFD1; CRF-1 supplemented with 16.5% fat, 1.25% cholesterol, and 0.5% sodium cholate; Oriental Yeast Co.) for 12 weeks from 8 weeks of age. Generation of Capn6- and Capn9-deficient mice was performed as described previously (20, 32). Capn6−/y mice express LacZ instead of CAPN6. Ldlr−/− mice (C57/BL6J) were obtained from The Jackson Laboratory (stock no. 2207). Capn6−/yLdlr−/− and Capn9−/−Ldlr−/− mice were generated by intercrossing Capn6−/y and Capn9−/− mice with Ldlr−/− mice, respectively. Capn6+/yLdlr−/−, Capn6−/yLdlr−/−, Capn9+/+Ldlr−/−, and Capn9−/−Ldlr−/− mice were maintained by homozygous breeding, as they have a common genetic background; the genotypes were determined by standard PCR-based genotyping with specific ...
Calpain-1 Substrate II, Fluorogenic - Calbiochem An internally quenched peptide substrate that is optimized for calpain-1 amino acid recognition motifs at the primed as well as the non-primed sides. - Find MSDS or SDS, a COA, data sheets and more information.
Please register to see prices including your discount. Registration may take up to 24h. For guest orders the standard discount of your institution will apply and discounts are visible on the order confirmation.. ...
Yorikawa C, Takaya E, Osako Y, Tanaka R, Terasawa Y, Hamakubo T, Mochizuki Y, Iwanari H, Kodama T, Maeda T et al. (2008) Human calpain 7/PalBH associates with a subset of ESCRT-III-related proteins in its N-terminal region and partly localizes to endocytic membrane compartments. J Biochem 143, 731-745 ...
The worlds first wiki where authorship really matters. Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts.
Complete information for CAPN10-AS1 gene (RNA Gene), CAPN10 Antisense RNA 1 (Head To Head), including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Reliable and easy to perform assays for studying the crucial role of alternative proteolytic enzymes during apoptosis. We offer various assays to detect and quantify cathepsin, calpain and granzyme B activity and screen for respective enzyme inhibitors.. ...
Order monoclonal and polyclonal Calpain 2 antibodies for many applications. Selected quality suppliers for anti-Calpain 2 antibodies.
Rabbit polyclonal Calpain 1 antibody validated for WB, IHC, ICC/IF and tested in Human, Mouse and Rat. Referenced in 14 publications. Immunogen corresponding…
Mouse polyclonal antibody raised against a full-length human CAPN12 protein. CAPN12 (AAI53094.1, 1 a.a. ~ 719 a.a) full-length human protein. (H00147968-B01P) - Products - Abnova
Characterizing Caplains Implications for production agriculture and human health Calpains and calpastatin may not be household words but their action is as clo
Malignant pleural mesothelioma (MPM), an aggressive malignant tumor of mesothelial origin associated with asbestos exposure, shows a limited response to conventional chemotherapy and radiotherapy. Therefore, the overall survival of MPM patients remains very poor. Progress in the development of therapeutic strategies for MPM has been limited. We recently reported that the calpain inhibitor, calpeptin exerted inhibitory effects on pulmonary fibrosis by inhibiting the proliferation of lung fibroblasts. In the present study, we examined the preventive effects of calpeptin on the cell growth of MPM, the origin of which is mesenchymal cells, similar to lung fibroblasts. Calpeptin inhibited the proliferation of MPM cells, but not mesothelial cells. It also prevented 1) the expression of angiopoietin (Ang)1 and Tie2 mRNA in MPM cells, but not mesothelial cells and 2) the Ang1induced proliferation of MPM cells through an NFkB dependent pathway, which may be the mechanism underlying the preventive effects of
Copyright 2013 by Don N. Tait. This material is copyrighted and any further reproduction or distribution is prohibited without the permission of the copyright owner ...
We present here evidence that the counterstimulatory chemokine IP-10 affects dermal fibroblast cell responses to growth factors in addition to its known actions on hematopoietic and endothelial cells. We demonstrated that IP-10 inhibits EGFR-mediated motility specifically, likely via a cAMP/PKA-dependent inhibition of EGFR-mediated calpain activation. To our knowledge, this is the first report of the inhibitory effects of IP-10 on growth factor-induced fibroblast motility. These actions implicate a role for IP-10 in limiting fibroblast infiltration during wound healing in response to locally expressed growth factors.. We determined that IP-10 did not disrupt EGFR signaling at the ligand or receptor level. This was expected as (a) both EGF- and HB-EGF-induced motility was similarly inhibited; and (b) EGFR-mediated proliferation was unaffected by IP-10 pretreatment. As cellular response signaling diverges at the immediate postreceptor level with at least one pathway, via PLC-γ, being required for ...
Here we have used postmortem brain from all Braak stages to examine at which stage of disease development changes occur in key neurodegenerative disease proteins. We demonstrate that there is increased activity of calpain-1 from Braak stage III onwards in comparison to controls, extending previous findings that calpain-1 is upregulated at end-stage disease. In addition, activation of the tau kinases, GSK-3 and cdk5 were also found to occur in Braak stage II-III tissues, and these preceded global elevations in tau phosphorylation and the loss of post-synaptic markers observed in late-stage AD. In addition, we identified transient increases in total APP and pre-synaptic markers in Braak stage II-III, that were lost by end-stage AD, that may be indicative of endogenous compensatory responses to the initial stages of neurodegeneration. Our human brain data substantiate findings from many experimental models which have supported the hypothesis that sporadic AD arises in response to Aβ-mediated ...
In the present study, the molecular mechanisms involved in the α‑tomatine‑induced apoptosis in human glioblastoma cell lines A172 and U‑118 MG were investigated. Wright staining and ApopTag assays were conducted to confirm the apoptosis induced by α‑tomatine treatment. Fura‑2 assay determined an enhancement in free Ca2+ intracellularly, indicating the occurrence of Ca2+‑dependent apoptosis induction. Western blot experiments were also performed to predict the apoptosis by measuring the changes in the Bax:Bcl‑2 ratio. Increase of calpain activity triggered caspase‑12 expression, which in turn further activated caspase‑9. In addition, an increase in the ratio of Bax:Bcl‑2 accounted for the mitochondrial release of cytochrome c into the cytosol for caspase‑3 and caspase‑9 activation. Elevated activity of calpain and caspase‑3 yielded spectrin breakdown products with 145 and 120 kDa, respectively. Caspase‑3 activation further cleaved the inhibitor of caspase activated ...
Conclusions. Lens gap junctions serve dual functions: one is to provide a pathway for metabolism and the other is to act as adhesion niches for the arrangement of surface interlocking structures required for lens transparency and stiffness. 129-Prx gene variance and CP49 deletion disrupted F-actin network or beaded intermediate filament to alter surface morphogenesis of lens fibers. Dysfunctional gap junctions and aberrant cytoskeletons synergistically impair lens homeostasis and the interlocking structures of maturing fibers, which trigger fiber cell degeneration mediated by calcium-dependent proteases, ultimately leading to dense nuclear cataracts. This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.. ...
TY - JOUR. T1 - Degradation of PEP-19, a calmodulin-binding protein, by calpain is implicated in neuronal cell death induced by intracellular Ca2+ overload. AU - Kanazawa, Y.. AU - Makino, M.. AU - Morishima, Y.. AU - Yamada, K.. AU - Nabeshima, T.. AU - Shirasaki, Y.. PY - 2008/6/23. Y1 - 2008/6/23. N2 - Excessive elevation of intracellular Ca2+ levels and, subsequently, hyperactivation of Ca2+/calmodulin-dependent processes might play an important role in the pathologic events following cerebral ischemia. PEP-19 is a neuronally expressed polypeptide that acts as an endogenous negative regulator of calmodulin by inhibiting the association of calmodulin with enzymes and other proteins. The aims of the present study were to investigate the effect of PEP-19 overexpression on cell death triggered by Ca2+ overload and how the polypeptide levels are affected by glutamate-induced excitotoxicity and cerebral ischemia. Expression of PEP-19 in HEK293T cells suppressed calmodulin-dependent signaling and ...
Glioblastoma multiforme is a form of primary brain cancer in humans with a 5 year survival rate of less than 4%. Glioblastoma cells are characterized by their highly invasive nature linked to mutations in key signaling proteins such as PTEN, resulting in loss of expression of this lipid phosphatase. When PTEN is not expressed, the phosphorylation and dephosphorylation equilibrium is disturbed resulting in elevated phosphatidylinositol 3,4,5-trisphosphate (PIP3) levels in the cell and constitutive activation of Akt. The Akt pathway, downstream of phosphoinositide 3-kinase production of PIP3, is known to be highly activated and involved in the progression of glioblastoma. Akt is activated by phosphorylation on Thr308 and Ser473 sites in a PIP3-dependent manner. We are examining calpain 2 proteolysis as a novel mechanism for modulating the activity of Akt. Understanding the regulation Akt may lead to new approaches for controlling the activity of a key promoter of cancer progression ...
This study was undertaken to determine the effects of inhibition of calpain on neurological deficit and neuronal apoptosis following experimental SAH....
|p| MDL 28170 is a selective inhibitor, which inhibites calpain with Ki values of 10nM and cathepsin B with Ki values of 25 nM while does not inhibit trypsin-like serine proteases. And it can penetrate the blood-brain barrier rapidly and show the activity
We investigated in vivo the chemotherapeutic anthracycline agents doxorubicin and its ability to activate mitochondrial-mediated, receptor-mediated and endoplasmic/sarcoplasmic reticulum-mediated apoptosis transduction pathways in cardiac tissue from male and female rats. We administered a single low dose of doxorubicin (10 mg/kg of body weight, i.p.) and then isolated mitochondrial and cytosolic proteins one and four days later from the heart. Caspase-3 protein content and caspase-3 activity were significantly increased after day four of doxorubicin treatment in both male and female rats. However, while males had DNA fragmentation at day one but not day four following doxorubicin administration, females showed no significant increase in DNA fragmentation at either time. Caspase-12, localized in the SR, is considered a central caspase, and its activation by cleavage via calpain indicates activation of the SR-mediated pathway of apoptosis. Cleaved caspase-12 content and calpain activity significantly
Androglobin (Adgb) is a recently discovered globin type consisting of large chimeric proteins with an N-terminal calpain-like protease domain and a central globin domain. Adgb is predominantly expressed in testis tissue and the expression is associated with the post-meiotic stages of spermatogenesis. Although we knew that Adgb plays a crucial role in male fertility, its molecular function is still not clear. The aim of this thesis was clear: unraveling the molecular function of Adgb. This was approached by using different strategies: the function was studied on biochemical, cellular and biological level.. To perform an in vitro biochemical characterization of the globin domain of Adgb, the globin domain was recombinantly expressed in E.coli, P.pastoris and baculovirus infected insect cells. We encountered difficulties with the solubility of the globin domain and concluded that for a proper folding it requires the context of the full length Adgb protein. Hence, we expressed the full length Adgb ...
Purpose: GSK-3 may regulate Wnt signaling, gene expression, the cell cycle, cell differentiation and apoptosis. Inhibition of GSK-3 can be obtained via the structurally unrelated substances lithum or Kenpaullone. The lens and the lens epithelial cells are excellent models to study the role of this enzyme. Methods: Primary cultures of human lens epithelial cells (HLEC) or the mouse lens in organ culture were exposed to the GSK-3 inhibitors lithium (2 mM) or Kenpaullone (2 {micro}M) for times upp to 24h.The cells were, before or after treatment, placed in medium containing fluorogenic indicators of oxidative damage. DCFH-DA was used to assay peroxides, mitochondrial function was evaluated with Rhodamine 123 and JC-1, monochlorobimane was used to assay intracellular glutathione (GSH) levels, Proteolytic activities were assayed, on line, with cell-permeable fluorogenic substrates.Proteasome and calpain activities were assayed with LLVY-AMC, Cathepsin B with RR-AMC or FR-AMC. Metalloproteases were ...
Learning, knowledge, research, insight: welcome to the world of UBC Library, the second-largest academic research library in Canada.
Abstracts of the 45th Annual Scientific Meeting of the European Society for Clinical Investigation Crete, Greece 13-16 April ...
The use of a neutral protease (NP) together with a collagenase consists in that a neutral protease which is not contained in a collagenase enzyme preparation and which is not produced by a recombinant
Calcium-regulated non-lysosomal thiol-protease which catalyze limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction.
Oxygen, Muscle, Skeletal Muscle, Apoptosis, Caspase-3, Cytochrome, Cytochrome C, DNA, DNA Fragmentation, Reactive Oxygen Species, Apoptosis-inducing Factor, Calpain, Cell, Cell Death, Death, Heat, Heat Shock Protein, Heat Shock Protein 70, Membrane, Membrane Potential
A team led by Tufts University researchers discovered that a communications breakdown between two biochemical pathways is involved in causing cataracts in mice. The newfound relationship between the ubiquitin and calpain pathways may lead to pharmaceuticals and dietary approaches that can prolong the function of the relevant pathways and delay the onset of cataracts in people.
Human CAPN14 full-length ORF (BAG52511.1, 1 a.a. - 508 a.a.) recombinant protein with GST-tag at N-terminal. (H00440854-P01) - Products - Abnova
Adequate carpi radialis muscle bulk for muscle biopsy as assessed by examination. Subjects should be able to communicate with the investigation staff. They should be able to understand, to comply with and to perform all needed evaluations during the trial period, including muscle strength tests. Forearm muscle strength should be of at least 3+ as assessed through the British Medical Research Council (MRC) Manual Muscle Testing (MMT) scale.. Subjects should also have already lost ambulation. ...
Some organophosphorus compounds (OP), including the pesticide mipafox, produce late onset distal axonal degeneration, known as organophosphorus-induced delayed neuropathy (OPIDN). The underlying mechanism involves irreversible inhibition of neuropathy target esterase (NTE) activity, elevated intracellular calcium levels, increased activity of calcium-activated proteases and impaired neuritogenesis. Voltage-gated calcium channels (VGCC) appear to play a role in several neurologic disorders, including OPIDN. Therefore, this study aimed to examine and compare the neuroprotective effects of T-type (amiloride) and L-type (nimodipine) VGCC blockers induced by the inhibitory actions of mipafox on neurite outgrowth and axonal proteins of retinoic-acid-stimulated SH-SY5Y human neuroblastoma cells, a neuronal model widely employed to determine the neurotoxicity attributed to OP ...
Mutations in human and/or mouse homologs are associated with this disease. Synonyms: LGMD2M; MDDGC4; muscular dystrophy-dystroglycanopathy (limb-girdle) type C 4
Ca(2+)-binding domain VI of rat calpain is a homodimer in solution: hydrodynamic, crystallization and preliminary X-ray diffraction studies
The limb‐girdle muscular dystrophies (LGMDs) area group of genetically heterogeneous neuromuscular disorders caused by specific protein defects in muscle fibres and characterised by predominant weakness and wasting in proximal limb and axial muscles
The CAPN3 gene is associated with autosomal recessive and dominant limb-girdle muscular dystrophy type 2A (LGMD2A) (MedGen UID: 358391; PMID:27259757).
1. Bergounioux J, Elisee R, Prunier AL, Donnadieu F, Sperandio B, Sansonetti P, et al. Calpain activation by the Shigella flexneri effector VirA regulates key steps in the formation and life of the bacteriums epithelial niche. Cell Host Microbe. 2012;11(3):240-52. doi: 10.1016/j.chom.2012.01.013 22423964.. 2. Carneiro LA, Travassos LH, Soares F, Tattoli I, Magalhaes JG, Bozza MT, et al. Shigella induces mitochondrial dysfunction and cell death in nonmyleoid cells. Cell Host Microbe. 2009;5(2):123-36. doi: 10.1016/j.chom.2008.12.011 19218084.. 3. Lembo-Fazio L, Nigro G, Noel G, Rossi G, Chiara F, Tsilingiri K, et al. Gadd45alpha activity is the principal effector of Shigella mitochondria-dependent epithelial cell death in vitro and ex vivo. Cell death & disease. 2011;2:e122. doi: 10.1038/cddis.2011.4 21368893; PubMed Central PMCID: PMC3101704.. 4. Miao EA, Mao DP, Yudkovsky N, Bonneau R, Lorang CG, Warren SE, et al. Innate immune detection of the type III secretion apparatus through the NLRC4 ...
Heat stress adversely affect broiler meat quality attributes particularly inducing more oxidation and toughness. Apoptosis is the process of mediated cell death occurring immediately after exsanguination of animals or stress conditions. It is initiated by release of cytochrome C to the cytoplasm, ultimately activating caspase 3. Since caspase 3 is an enzyme that cleaves calpastatin, a known inhibitor of calpain (primary proteolytic enzyme), a potential involvement of apoptosis in meat tenderness development has been proposed. Therefore, in this study, we aimed to further investigate the role of apoptosis in the postmortem meat tenderization and oxidation stability using the heat-stress broiler model ...
As a forum for professional feedback, submissions of letters are open to all. You do not need to be a subscriber. To avoid redundancy, we urge you to read other peoples letters before submitting your own. Name, current appointment, place of work, and email address are required to send a letter, and will be published with your review. We also require that you declare any competing financial interests. Unprofessional submissions will not be considered or responded to.. ...
Principal Investigator:SHIMIZU Katsuji, Project Period (FY):1998 - 1999, Research Category:Grant-in-Aid for Scientific Research (B), Section:一般, Research Field:Orthopaedic surgery
... is a calcium-binding protein of the sarcoplasmic reticulum. The protein helps hold calcium in the cisterna of the sarcoplasmic reticulum after a muscle contraction, even though the concentration of calcium in the sarcoplasmic reticulum is much higher than in the cytosol. It also helps the sarcoplasmic reticulum store an extraordinarily high amount of calcium ions. Each molecule of calsequestrin can bind 18 to 50 Ca2+ ions.[1] Sequence analysis has suggested that calcium is not bound in distinct pockets via EF-hand motifs, but rather via presentation of a charged protein surface. Two forms of calsequestrin have been identified. The cardiac form Calsequestrin-2 (CASQ2) is present in cardiac and slow skeletal muscle and the fast skeletal form Calsequestrin-1(CASQ1) is found in fast skeletal muscle. The release of calsequestrin-bound calcium (through a calcium release channel) triggers muscle contraction. The active protein is not highly structured, more than 50% of it adopting a ...
Calpain 8 is a protein in humans that is encoded by the CAPN8 gene. GRCh38: Ensembl release 89: ENSG00000203697 - Ensembl, May ...
Calpain (2017-06-21). "(AU) MLP Season 7 Episode 13 - The Perfect Pear - Stream / Discussion". Equestria Daily. Retrieved 2017- ...
Calpain 6 is a protein in humans that is encoded by the CAPN6 gene. Calpains are ubiquitous, well-conserved family of calcium- ... The calpain proteins are heterodimers consisting of an invariant small subunit and variable large subunits. The large subunit ... Calpains have been implicated in neurodegenerative processes, as their activation can be triggered by calcium influx and ... Its C-terminal region lacks any homology to the calmodulin-like domain of other calpains. The protein lacks critical active ...
Calpain (October 5, 2016). "(It Aired!) UK - Season 6 Episode 25 - To Where and Back Again - Stream / Discussion (It Aired!)". ... Calpain (2017-06-21). "(AU) MLP Season 7 Episode 13 - The Perfect Pear - Stream / Discussion". Equestria Daily. Retrieved 2017- ...
Calpain-9 is a protein that in humans is encoded by the CAPN9 gene. Calpains are ubiquitous, well-conserved family of calcium- ... "Entrez Gene: CAPN9 calpain 9". Huang Y, Wang KK (2001). "The calpain family and human disease". Trends in Molecular Medicine. 7 ... The calpain proteins are heterodimers consisting of an invariant small subunit and variable large subunits. The large subunit ... Calpains have been implicated in neurodegenerative processes, as their activation can be triggered by calcium influx and ...
"Ionomycin-activated calpain triggers apoptosis. A probable role for Bcl-2 family members". The Journal of Biological Chemistry ...
Calpain-2 catalytic subunit is a protein that in humans is encoded by the CAPN2 gene. The calpains, calcium-activated neutral ... m-calpains and calpastatin and capture of mu-calpain activation in endothelial cells". J. Cell. Biochem. 66 (2): 197-209. doi: ... "Entrez Gene: CAPN2 calpain 2, (m/II) large subunit". Gil-Parrado S, Fernández-Montalván A, Assfalg-Machleidt I, Popp O, ... Potential role of calpain, protein tyrosine phosphatase 1b, and p130Cas in integrin-mediated signaling events". J. Biol. Chem. ...
Löfvenberg L, Backman L (1999). "Calpain-induced proteolysis of beta-spectrins". FEBS Lett. 443 (2): 89-92. doi:10.1016/S0014- ...
Calpain-3 is a protein that in humans is encoded by the CAPN3 gene. Calpain, a heterodimer consisting of a large and a small ... "Entrez Gene: CAPN3 calpain 3, (p94)". Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir ... Huang Y, de Morrée A, van Remoortere A, Bushby K, Frants RR, den Dunnen JT, van der Maarel SM (2008). "Calpain 3 is a modulator ... Ohno S, Minoshima S, Kudoh J, Fukuyama R, Shimizu Y, Ohmi-Imajoh S, Shimizu N, Suzuki K (1990). "Four genes for the calpain ...
Calpain small subunit 1, also known as CAPN4, is a protein that in humans is encoded by the CAPNS1 gene. Calpains are a ... Calpain I and II are heterodimeric with distinct large subunits associated with common small subunits, all of which are encoded ... "Entrez Gene: CAPNS1 calpain, small subunit 1". Zhuang Q (Apr 2014). "Capn4 mRNA level is correlated with tumour progression and ... Calpain families have been implicated in neurodegenerative processes, as their activation can be triggered by calcium influx ...
1997). "Identification of mu-, m-calpains and calpastatin and capture of mu-calpain activation in endothelial cells". J. Cell. ... 1989). "Inhibition of calpain by a synthetic oligopeptide corresponding to an exon of the human calpastatin gene". J. Biol. ... The calpain/calpastatin system is involved in numerous membrane fusion events, such as neural vesicle exocytosis and platelet ... It consists of an N-terminal domain L and four repetitive calpain-inhibition domains (domains 1-4), and it is involved in the ...
"Tyrosine phosphorylation regulates alpha II spectrin cleavage by calpain". Mol. Cell. Biol. 22 (10): 3527-36. doi:10.1128/MCB. ...
Calpain-1 catalytic subunit is a protein that in humans is encoded by the CAPN1 gene. The calpains, calcium-activated neutral ... "Entrez Gene: CAPN1 calpain 1, (mu/I) large subunit". Shinozaki K, Maruyama K, Kume H, Tomita T, Saido TC, Iwatsubo T, Obata K ( ... The mammalian calpains include ubiquitous, stomach-specific, and muscle-specific proteins. The ubiquitous enzymes consist of ... This gene encodes the large subunit of the ubiquitous enzyme, calpain 1. CAPN1 has been shown to interact with PSEN2. GRCh38: ...
This protein is a substrate of calpain II. A second transcript from this gene has been described, but its full length nature ...
The protease calpain has also been shown to be involved in this type of cell destruction; just as the use of calpain inhibitors ... Wang KK (Jan 2000). "Calpain and caspase: can you tell the difference?". Trends in Neurosciences. 23 (1): 20-6. doi:10.1016/ ... Villa PG, Henzel WJ, Sensenbrenner M, Henderson CE, Pettmann B (Mar 1998). "Calpain inhibitors, but not caspase inhibitors, ...
These cysteine proteases include calpain, caspase, and cathepsin. These three proteins are examples of detectable signs of ...
This group includes the calpains. Basic proteases (or alkaline proteases) Proteases are involved in digesting long protein ...
Calpain-5 is a protein that in humans is encoded by the CAPN5 gene. Calpains are calcium-dependent cysteine proteases involved ... "Entrez Gene: CAPN5 calpain 5". Vanderklish PW, Bahr BA (2001). "The pathogenic activation of calpain: a marker and mediator of ... A functional calpain protein consists of an invariant small subunit and 1 of a family of large subunits. CAPN5 is one of the ... 2007). "Calpain-5 gene variants are associated with diastolic blood pressure and cholesterol levels". BMC Med. Genet. 8: 1. doi ...
... interacts with many sarcomeric proteins including: Z line region: telethonin and alpha-actinin I band region: calpain-3 ... Kinbara K, Sorimachi H, Ishiura S, Suzuki K (August 1998). "Skeletal muscle-specific calpain, p49: structure and physiological ... Sorimachi H, Ono Y, Suzuki K (2000). "Skeletal muscle-specific calpain, p94, and connectin/titin: their physiological functions ... "Muscle-specific calpain, p94, responsible for limb girdle muscular dystrophy type 2A, associates with connectin through IS2, a ...
... undergoes N-terminal cleavage by Calpain-1 and Calpain-2. The cleaved ATG5 translocates from the cytosol to the ... Yousefi S, Perozzo R, Schmid I, Ziemiecki A, Schaffner T, Scapozza L, Brunner T, Simon HU (October 2006). "Calpain-mediated ...
Calpain-10 is a protein that in humans is encoded by the CAPN10 gene. Calpains are ubiquitous, well-conserved family of calcium ... "Entrez Gene: CAPN10 calpain 10". Sorimachi H, Ishiura S, Suzuki K (1998). "Structure and physiological function of calpains". ... 2001). "Characterization and expression of calpain 10. A novel ubiquitous calpain with nuclear localization". J. Biol. Chem. ... Horikawa Y (2007). "Calpain-10 (NIDDM1) as a Susceptibility Gene for Common Type 2 Diabetes". Endocr. J. 53 (5): 567-76. doi: ...
One possibility is that the calcium-dependent protease calpain is involved: it has been shown that the inhibition of calpain ... Focal adhesion components are amongst the known calpain substrates, and it is possible that calpain degrades these components ... "Regulation of cell migration by the calcium-dependent protease calpain". Journal of Biological Chemistry. 272 (52): 32719-22. ...
Baliova M, Betz H, Jursky F (2004). "Calpain-mediated proteolytic cleavage of the neuronal glycine transporter, GlyT2". J. ...
Synuclein Inclusions via the Activation of Calpain". Journal of Biological Chemistry. 278 (43): 41890-9. doi:10.1074/jbc. ...
As the first calpain whose three-dimensional structure was determined, m-calpain is the type-protease for the C2 (calpain) ... calpain and m-calpain (or calpain I and II), that differed primarily in their calcium requirements in vitro. Their names ... Calpain for Modulatory Proteolysis Database The Calpain Family of Proteases. (2001). University of Arizona. Calpain Info with ... Calpains constitute the C2 family of protease clan CA in the MEROPS database. The calpain proteolytic system includes the ...
Calpastatin (CAST) is a calpain inhibitor, a calcium-dependent cysteine protease that is widely distributed in higher order ... Through its inhibition of calpain, calpastatin is believed to play important roles in the regulation of cell proliferation, ...
Calpain 8/nCL-2 and calpain 9/nCL-4 constitute an active protease complex, G-calpain, involved in gastric mucosal defense.. ... The calpain system.. Physiol. Rev. 83 731-801 2003. Jeong SY, Martchenko M, Cohen SN. Calpain-dependent cytoskeletal ... Calpain-9 (CAPN9) belongs to the calpain family, which consists of a group of Ca2+ dependent cysteine proteases that regulate ... Calpain-9 and Calpain-8 are predominantly expressed in the gastrointestinal tract and are restricted to the gastric surface ...
A single C2 domain is found in calpains (EC 3.4.22.52, EC 3.4.22.53), calcium-dependent, non-lysosomal cysteine proteases. ...
Calpains are a family of Ca2+-dependent cysteine proteases that play a key role in multiple cell functions including cell ... Calpain Dysregulation in Alzheimers Disease. Adriana Ferreira Department of Cell and Molecular Biology, Feinberg School of ... One of such mechanisms seems to be the dysregulation of calcium homeostasis that results in the abnormal activation of calpains ... We also summarized data underscoring the participation of calpains in the neurodegenerative mechanisms associated with AD. ...
Domain I of the large subunit of Calpain 1; does not recognize N-processed Calpain 1, and can be used to discriminate between ... Immunogen = synthetic peptide based on domain-I in the large subunit of human Calpain 1 ...
If you know of any papers that use this antibody, please contact us at antibodies [at] alzforum [dot] org for consideration in the References section.. ...
... no cross reaction with the other calpain family members (M Calpain, Calpain 94, ncl2, ncl3, etc.) ... binds to the N-terminal end of domain-III and recognizes latent and amino-processed Calpain-10; ...
C2_Calpain; C2 domain present in Calpain proteins. cd00214. Location:352 → 498. Calpain_III; Calpain, subdomain III. Calpains ... C2_Calpain; C2 domain present in Calpain proteins. cd00214. Location:352 → 498. Calpain_III; Calpain, subdomain III. Calpains ... C2_Calpain; C2 domain present in Calpain proteins. pfam01067. Location:394 → 533. Calpain_III; Calpain large subunit, domain ... calpain-5. Names. calpain htra-3. new calpain 3. testis tissue sperm-binding protein Li 91mP. ...
Calpain-2 (EC 3.4.22.53, calcium-activated neutral protease II, m-calpain, milli-calpain) is an enzyme. This enzyme catalyses ... and m-calpain". Biochem. J. 367: 263-269. doi:10.1042/bj20020485. PMC 1222847 . PMID 12014988. Calpain-2 at the US National ... "The crystal structure of calcium-free human m-calpain suggests an electrostatic switch mechanism for activation by calcium". ...
Calpain-1 (EC 3.4.22.52, mu-calpain, calcium-activated neutral protease I) is an enzyme. This enzyme catalyses the following ... and m-calpain". Biochem. J. 367: 263-269. doi:10.1042/bj20020485. PMC 1222847 . PMID 12014988. Calpain-1 at the US National ...
Calpain-3 (EC 3.4.22.54, p94, calpain p94, CAPN3, muscle calpain, calpain 3, calcium-activated neutral proteinase 3, muscle- ... Calpain-3 at the US National Library of Medicine Medical Subject Headings (MeSH) Molecular and Cellular Biology portal. ... Rey, M.A.; Davies, P.L. (2002). "The protease core of the muscle-specific calpain, p94, undergoes Ca2+-dependent intramolecular ... García Díaz, B.E.; Gauthier, S.; Davies, P.L. (2006). "Ca2+ dependency of calpain 3 (p94) activation". Biochemistry. 45 (11): ...
Calpain-mediated proteolysis of talin regulates adhesion dynamics.. Franco SJ1, Rodgers MA, Perrin BJ, Han J, Bennin DA, ... Here, we show that proteolysis of talin by the intracellular calcium-dependent protease calpain is critical for focal adhesion ... We have generated a single point mutation in talin that renders it resistant to proteolysis by calpain. Quantification of ... Together, these findings identify calpain-mediated proteolysis of talin as a mechanism by which adhesion dynamics are regulated ...
... Calpains (EC 3.4.22.52, EC 3.4.22.53) are a family of calcium-dependent, non-lysosomal cysteine proteases (proteolytic ... calpain and m-calpain (a.k.a. calpain I and II), that differed primarily in their calcium requirements in vitro. Their names ... Calpains in pathologies The structural and functional diversity of calpains in the cell is reflected in their involvement in ... As the first calpain whose almost complete three-dimensional structure was determined, m-calpain is the type-protease for the ...
Calpain Inhibitor II for your research needs. Find product specific information including CAS, MSDS, protocols and references. ... Calpain I, Calpain I Inhibitors, Calpain II, Calpain II Inhibitors, Calpain Inhibitors, Calpain and Proteasome Inhibitors, ... Calpain inhibitor II is a cell-permeable peptide that restricts the activity of calpain, cathepsin L and cathepsin B. Calpain ... Calpain Inhibitor II powder Synonym: N-Acetyl-. L. -leucyl-. L. -leucyl-. L. -methioninal ...
E-64c Calpain Inhibitor; CAS Number: 76684-89-4; Synonym: (2S,3S)-trans-Epoxysuccinyl-L-leucylamido-3-methylbutane; Linear ... A to C, Apoptosis Enzymes, Application Index, Biochemicals and Reagents, Calpain, Calpain II, Calpain II Inhibitors, Calpain ... Cysteine protease inhibitor; membrane-impermeable calpain inhibitor. Significantly reduces calpain-mediated depletion of ...
... crystal structures of the native domain VI of calpain and its complexes with calpastatin peptide and a small molecule inhibitor ... A structural model for the inhibition of calpain by calpastatin: ... Calpain Domain VI. *DOI: 10.2210/pdb1nx2/pdb. *Classification: ...
The authors propose that activation of calpain by an increase in intracellular calcium, a condition that also promotes calpain ... Activation of caspase-12 in glial cells, in response to ER stress agents, was blocked when cells were treated with a calpain ... Nakagawa, T., and Yuan, J. (2000) Cross-talk between two cysteine protease families: Activation of caspase-12 by calpain in ... is cleaved and activated by a noncaspase protease called calpain. ...
Rabbit polyclonal Calpain 1 antibody validated for WB, ICC/IF and tested in Human, Mouse and Rat. Referenced in 9 publications ... Also, it does not cross react with the other calpain family members (M Calpain, Calpain 94, ncl2, ncl3, etc.). ... All lanes : Anti-Calpain 1 antibody (ab28257) at 1 µg/ml. Lane 1 : Human liver tissue lysate - total protein (ab29889). Lane 2 ... Calpain 1 regulates TGF-ß1-induced epithelial-mesenchymal transition in human lung epithelial cells via PI3K/Akt signaling ...
Rabbit polyclonal Calpain 1 antibody validated for WB, IHC, ICC/IF and tested in Human, Mouse and Rat. Referenced in 14 ... Calpain 1. It but does not cross react with the other calpain family members (Calpain 2, calpain 94, ncl 2, ncl 3, etc.). ... This antibody binds to reduced and non reduced Calpain 1. It reacts with Domain IV of Calpain 1, and detects both latent and ... The calpain-suppressing effects of olesoxime in Huntingtons disease.. Rare Dis 4:e1153778 (2016). WB . Read more (PubMed: ...
Rabbit polyclonal Calpain 5 antibody. Validated in WB, ICC/IF and tested in Mouse, Rat, Human. Cited in 2 publication(s). ... Does not cross react with the other calpain family members (Calpain 1, Calpain 2, Calpain 3, ncl 3, etc.). ... Calpain-5 Expression in the Retina Localizes to Photoreceptor Synapses.. Invest Ophthalmol Vis Sci 57:2509-21 (2016). Read more ... Calpain 5 is highly expressed in the central nervous system (CNS), carries dual nuclear localization signals, and is associated ...
IPR022684 Calpain_cysteine_protease. IPR029545 CAPN12. IPR038765 Papain-like_cys_pep_sf. IPR001300 Peptidase_C2_calpain_cat. ... IPR022684 Calpain_cysteine_protease. IPR029545 CAPN12. IPR038765 Papain-like_cys_pep_sf. IPR001300 Peptidase_C2_calpain_cat. ... Calpain-12Imported. ,p>Information which has been imported from another database using automatic procedures.,/p> ,p>,a href="/ ... Calpain catalyticInterPro annotation. ,p>Information which has been generated by the UniProtKB automatic annotation system, ...
Mouse monoclonal Calpain 2 antibody [1E8] validated for WB, ELISA, ICC/IF and tested in Human and Cow. With 1 independent ... Immunoflurescence of intracellular calpain in bovine lens epithel cells using MAb 1E8 (green). ... Recognises a linear epitope of the 80 kDa (large) subunit of bovine m-calpain ...
Non-caspase proteases such as calpains and cathepsins play an important role in cell death. Learn more about how to detect ... Calpains. ​Calpains are cytosolic calcium-dependent cysteine proteases composed of one or two subunits. Calpain cleavage sites ... Calpain activity assay (ab65308): Calpain activity measured in Jurkat cells in the absence (naïve) or presence of 10 μM ... Calpain activity can be easily detected in many cell types using a specific calpain substrate linked to a colorimetric or ...
... suppression of calpain expression with siRNAs against μ-calpain or m-calpain and inhibition of calpain activation by specific ... or m-calpain siRNA (lane 4) and processed on DIV 4 for immunoblotting with anti-m-calpain (arrow indicates native m-calpain, Mr ... In Vitro m-Calpain-Mediated p53 Cleavage Assay.. Purified m-calpain (0.5 U/mL; Calbiochem) and CaCl2 (1.0 mM; Sigma) were added ... Calpain, and in particular m-calpain, is ideally suited to integrate these various signals, as a result of its dual regulation ...
  • Structurally, these two heterodimeric isoforms share an identical small (28 k) subunit (CAPNS1 (formerly CAPN4)), but have distinct large (80 k) subunits, known as calpain 1 and calpain 2 (each encoded by the CAPN1 and CAPN2 genes, respectively). (wikipedia.org)
  • When the sequence of this enzyme became known, it was given the name "calpain", to recognize it as a hybrid of two well-known proteins at the time, the calcium-regulated signalling protein, calmodulin, and the cysteine protease of papaya, papain. (wikipedia.org)
  • Calpain is also involved in skeletal muscle protein breakdown due to exercise and altered nutritional states. (wikipedia.org)
  • Under these physiological conditions, a transient and localized influx of calcium into the cell activates a small local population of calpains (for example, those close to Ca2+ channels), which then advance the signal transduction pathway by catalyzing the controlled proteolysis of its target proteins. (wikipedia.org)
  • When defective, the mammalian calpain 3 (also known as p94) is the gene product responsible for limb-girdle muscular dystrophy type 2A, calpain 10 has been identified as a susceptibility gene for type II diabetes mellitus, and calpain 9 has been identified as a tumour suppressor for gastric cancer. (wikipedia.org)
  • Although the physiological role of calpains is still poorly understood, they have been shown to be active participants in processes such as cell mobility and cell cycle progression, as well as cell-type specific functions such as long-term potentiation in neurons and cell fusion in myoblasts. (wikipedia.org)
  • Shortly thereafter, the activity was found to be attributable to two main isoforms, dubbed μ ("mu")-calpain and m-calpain (or calpain I and II), that differed primarily in their calcium requirements in vitro. (wikipedia.org)
  • Enhanced calpain activity, regulated by CAPNS1, significantly contributes to platelet hyperreactivity under hypoxic environment. (wikipedia.org)
  • The Human Genome Project has revealed that more than a dozen other calpain isoforms exist, some with multiple splice variants. (wikipedia.org)
  • The structural and functional diversity of calpains in the cell is reflected in their involvement in the pathogenesis of a wide range of disorders. (wikipedia.org)
more