Apoptosis is a process of fundamental importance to multicellular organisms that enables control of cell populations and the removal of damaged or potentially harmful cells (Arends and Wyllie 1991). Apoptosis occurs in two phases: an initial commitment phase followed by an execution phase involving cytoskeletal disruption, membrane blebbing, condensation and fragmentation of chromatin, and the formation of apoptotic bodies (Earnshaw 1995). Caspases, a family of aspartate-specific cysteine proteases, play a critical role in the execution phase of apoptosis and are the key effectors responsible for many of the dramatic morphological and biochemical changes of apoptosis (for reviews see Cohen 1997; Thornberry and Lazebnik 1998). Caspases are proteolytically cleaved at specific aspartate residues, generating a large and small subunit that together form the active enzyme. Caspases can be divided into two classes: (1) initiator caspases, with long prodomains, such as caspases-8 and -9, which either ...

A very important goal is to determine which molecular components may be used in the execution of programmed cell death (PCD) in plants, which have been conserved during evolution and which are plant specific. Using A. thaliana we have shown that UV radiation can induce apoptotic-like changes at the cellular level and that an UV experimental system was relevant to the study of PCD in plants. UV induction of PCD requires light and a protease cleaving the caspase substrate Asp-Glu-Val-Asp (DEVDase activity) is induced within 30 minutes and peaks at one hour. This DEVDase appears related to animal caspases at the biochemical level, being insensitive to broad-range cysteine protease inhibitors. In addition, caspase1, caspase-3 inhibitors and the pancaspase inhibitor p35 were able to suppress DNA fragmentation and cell death. These results suggest that a YVADase (Tyr-Val-Ala-Asp) activity and an inducible DEVDase activity are possibly mediating DNA fragmentation during plant PCD induced by UV ...

Fingerprint Dive into the research topics of Casiopeina III-ia induces apoptosis in HCT-15 cells in vitro through caspase-dependent mechanisms and has antitumor effect in vivo. Together they form a unique fingerprint. ...

We used cytoplasmic extracts from chicken DU249 cells at various stages along the apoptotic pathway to analyse the events of apoptotic exe-cution. So-called S/M extracts from morphologically normal committed-stage cells induce apoptotic morphology and DNA cleavage in substrate nuclei. These apoptotic changes appear to require the function of multiple caspases (cysteine aspar-tases, a specialized class of proteases) acting in parallel. Extracts from execution-stage apoptotic cells induce apoptotic events in added nuclei in a caspase-independent manner. Biochemical frac-tionation of these extracts reveals that a column fraction enriched in endogenous active caspases is un-able to induce DNA fragmentation or chromatin condensation in substrate nuclei, whereas a caspase-depleted fraction induces both changes. Execution-stage extracts contain an ICAD/DFF45-inhibitable nuclease resembling CAD, plus another activity that is required for the apoptotic chromatin condensation. Committed-stage S/M ...

Caspases, aspartate-specific cysteine proteases, have fate-determining roles in many cellular processes including apoptosis, differentiation, neuronal remodeling, and inflammation (for review, see Yuan & Kroemer, 2010). There are a dozen caspases in humans alone, yet their individual contributions toward these phenotypes are not well understood. Thus, there has been considerable interest in activating individual caspases or using their activity to drive these processes in cells and animals. We envision that such experimental control of caspase activity can not only afford novel insights into fundamental biological problems but may also enable new models for disease and suggest possible routes to therapeutic intervention. In particular, localized, genetic, and small-molecule-controlled caspase activation has the potential to target the desired cell type in a tissue. Suppression of caspase activation is one of the hallmarks of cancer and thus there has been significant enthusiasm for generating ...

© 2015 Wiley-VCH Verlag GmbH & Co. KGaA,. All rights reserved. This chapter highlights the prevalence of protein kinase signaling in apoptotic pathways and emphasizes the emergence of global strategies to systematically investigate bidirectional crosstalk between protein kinase phosphorylation and caspase-mediated proteolysis in the propagation of irreversible apoptotic induction. Caspases are classified as cysteine proteases that catalyze irreversible cleavage of peptide bonds C-terminal to aspartic acid residues. The apoptotic role of protein kinases is of interest because posttranslational phosphorylation of both caspases and caspase substrates affects caspase functionality, and conversely, a variety of protein kinases are proteolytically digested by caspases to facilitate or prevent apoptosis. Throughout this chapter, examples have been provided highlighting the complex interactions between protein kinases and caspases that facilitate the progression of apoptosis. The emergence of novel

Caspases are key components of apoptotic pathways. Regulation of caspases occurs at several levels, including transcription, proteolytic processing, inhibition of enzymatic function, and protein degradation. In contrast, little is known about the extent of post-transcriptional control of caspases. Here, we describe four conserved RNA-binding proteins (RBPs)-PUF-8, MEX-3, GLD-1, and CGH-1-that sequentially repress the CED-3 caspase in distinct regions of the Caenorhabditis elegans germline. We demonstrate that GLD-1 represses ced-3 mRNA translation via two binding sites in its 3′ untranslated region (UTR), thereby ensuring a dual control of unwanted cell death: at the level of p53/CEP-1 and at the executioner caspase level. Moreover, we identified seven RBPs that regulate human caspase-3 expression and/or activation, including human PUF-8, GLD-1, and CGH-1 homologs PUM1, QKI, and DDX6. Given the presence of unusually long executioner caspase 3′ UTRs in many metazoans, translational control of ...

Caspases are a conserved family of cysteine proteases. They play diverse roles in inflammatory responses and apoptotic pathways. Among the caspases is a subgroup whose primary function is to initiate apoptosis. Within their long prodomains, caspases-2, -9 and -12 contain a caspase activation and recruitment domain while caspases-8 and -10 bear death effector domains. Activation follows the recruitment of the procaspase molecule via the prodomain to a high molecular mass complex. Despite sharing some common features, other aspects of the biochemistry, substrate specificity, regulation and signaling mechanisms differ between initiator apoptotic caspases. Defects in expression or activity of these caspases are related to certain pathological conditions including neurodegenerative disorders, autoimmune diseases and cancer ...

Follicle cells undergo premature caspase-dependent cell death in lrrk NS flies. (A) Schematic depicting a stage-12 egg chamber, with anterior to the left and po

In previous study we showed that caspase-2 plays the role of an apical caspase in cell death induction by taxanes in breast cancer cells. This study deals with the role of other caspases. We tested breast cancer cell lines SK-BR-3 (functional caspase-3) and MCF-7 (nonfunctional caspase-3). Using western blot analysis we demonstrated the activation of initiator caspase-8 and -9 as well as executioner caspase-6 and -7 in both tested cell lines after application of taxanes (paclitaxel, SB-T-1216) at death-inducing concentrations. Caspase-3 activation was also found in SK-BR-3 cells. Employing specific siRNAs after taxane application, suppression of caspase-3 expression significantly increased the number of surviving SK-BR-3 cells. Inhibition of caspase-7 expression also increased the number of surviving SK-BR-3 and MCF-7 cells. On the other hand, suppression of caspase-8 and caspase-9 expression had no significant effect on cell survival. However, caspase-9 seemed to be involved in the activation of

Apoptosis is a major form of cell death, characterized initially by a series of stereotypic morphological changes. In the nematode Caenorhabditis elegans, the gene ced-3 encodes a protein required for developmental cell death. Since the recognition that CED-3 has sequence identity with the mammalian cysteine protease interleukin-1β-converting enzyme (ICE), a family of at least 10 related cysteine proteases has been identified. These proteins are characterized by almost absolute specificity for aspartic acid in the P1 position. All the caspases (ICE-like proteases) contain a conserved QACXG (where X is R, Q or G) pentapeptide active-site motif. Caspases are synthesized as inactive proenzymes comprising an N-terminal peptide (prodomain) together with one large and one small subunit. The crystal structures of both caspase-1 and caspase-3 show that the active enzyme is a heterotetramer, containing two small and two large subunits. Activation of caspases during apoptosis results in the cleavage of ...

Generic Caspase Activity Assay Kit (Fluorometric - Green) (ab112130). Detect generic caspase activation in live cells with green TF2-VAD-FMK substrate.

An executor is the personal representative of your estate. They are the person in charge of taking control of your assets, paying off any debts, and distributing assets to your beneficiaries per the terms and conditions of your will. You can choose anyone to be the executor of your will, but it is a good idea to choose someone who is both competent and trustworthy. The person you choose to be executor should be outlined in your will. Someone you appoint to be the executor of your will has the right to refuse, so you should have a backup executor in place just in case. ...

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Pyroptosis is a unique, pro‐inflammatory form of lytic cell death that is initiated by the activation of inflammatory caspases. The caspase substrate gasdermin D (GSDMD) plays a critical function in pyroptosis, yet the precise mode of action of this molecule in cell death execution remained unclear. Several recent reports, including a The EMBO Journal article, show that the caspase‐matured N‐terminal fragment of GSDMD is recruited to lipid membranes to form pore‐like structures, which constitutes the key effector mechanism of pyroptotic cell death.. See also: L Sborgi et al (August 2016) ...

Apoptosis or programmed death is a physiological process responsible for normal development and homeostasis of multicellular organisms. This process involves a well-functioning machinery of death, which are the main component of cysteine ​​proteases - caspases family. These enzymes are present in cells in a latent form and become activated during apoptosis induced by various factors. This review summarizes the progress made on structure, mechanism of activation, catalytic properties, are substrates of caspases and regulation of their activity. Also shown in the involvement of caspases in the major pathways of apoptosis.. ...

Detail záznamu - Role of Caspases and CD95/Fas in the Apoptotic Effects of a Nucleotide Analog PMEG in CCRF-CEM Cells - Detail záznamu - Knihovna Akademie věd České republiky

Apoptosis, the most abundant form of programmed cell death during metazoan development, is executed by proteases called caspases. Efforts of many research groups have led to a deep understanding of how caspases are activated and regulated during apoptotic cell death. However, a constantly growing body of research has uncovered new caspase-dependent non-lethal cellular processes (CDPs), of which the molecular regulatory and executional mechanisms are much less understood. CDPs have been reported to modulate many basic cellular processes, such as signaling, proliferation, differentiation, remodeling and neuronal plasticity in a large variety of cell types and organisms. Unsurprisingly, this functional diversity of CDPs might trigger and sustain a wide range of diseases, including cancer and neurodegenerative disorders. Furthermore, it is perceived that caspase-regulating molecules could be a promising avenue for developing new therapeutic strategies. Given the recent explosion of reports and the ...

This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein can undergo autoproteolytic processing and activation by the apoptosome, a protein complex of cytochrome c and the apoptotic peptidase activating factor 1; this step is thought to be one of the earliest in the caspase activation cascade. This protein is thought to play a central role in apoptosis and to be a tumor suppressor. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013 ...

Downstream activation of caspases and enhanced phosphatidylserine (PS) exposure after long-term blockage of NMDAR in differentiating EPCs. EPCs obtained from th

The Proteasome-Glo™ Cell-Based Assays are homogeneous, luminescent assays that measure the chymotrypsin-like, trypsin-like and caspase-like protease activities associated with the proteasome complex in cultured cells.

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I am curious about something. People with CFS have been shown to have higher than normal levels of apoptosis (programmed cell death). According to...

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CASP1 - CASP1 (untagged)-Human caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) (CASP1), transcript variant gamma available for purchase from OriGene - Your Gene Company.

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First, the up to date Ensembl IDs have been retrieved for the many genes with SD three between rapamycin and Ly294002 therapies. The Amuvatinib 溶解度 GO lessons

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TY - JOUR. T1 - Cloning and expression of rat caspase-6 and its localization in renal ischemia/reperfusion injury. AU - Singh, Amar B.. AU - Kaushal, Varsha. AU - Megyesi, Judit K.. AU - Shah, Sudhir V.. AU - Kaushal, Gur P.. PY - 2002/1/1. Y1 - 2002/1/1. N2 - Background. Caspase-6 is an important member of the executioner caspases in the caspase family of cell death proteases. The executioner caspases are the major active caspases detected in apoptotic cells and are generally considered to mediate the execution of apoptosis by cleaving and inactivating intracellular proteins. However, the complete characterization of mRNA and protein of caspase-6 in rat and its expression in normal kidney and in disease state has not been previously elucidated. Methods. A rat kidney cortex λgt10 cDNA library was screened to isolate the full-length caspase-6 cDNA. The recombinant caspase-6 protein was characterized by expression in bacteria and by transient transfection in mammalian cells. The expression in ...

Psoriasis is a chronic autoimmune disorder of the skin. In this disease, the inflammatory caspases, cysteine proteases involved in the processing of many proteins, are activated. Transgenic mice expressing the cleaved form of caspases by Lyn, a tyrosine kinase Src family, develop an inflammatory syndrome with the characteristics of human psoriasis.. To clarify the relationship between the cleaved form of Lyn by caspases and psoriasis, the investigators intend to develop a clinical study to analyze the expression, cleavage and activity of Lyn and the activation of caspases from skin biopsies of patients with this disease.. This study will be conducted on a cohort of patients with different forms of psoriasis (plaque, pustular and erythrodermic) and atopic dermatitis, another skin disorder associated with chronic inflammation. Thus, the investigators will evaluate the expression and activity of Lyn from skin lesion (L) and non-lesional (NL) from the same patient in parallel with the level of ...

1. WelchmanRLGordonCMayerRJ 2005 Ubiquitin and ubiquitin-like proteins as multifunctional signals. Nat Rev Mol Cell Biol 6 599 609. 2. HickeLSchubertHLHillCP 2005 Ubiquitin-binding domains. Nat Rev Mol Cell Biol 6 610 621. 3. ChenZJSunLJ 2009 Nonproteolytic functions of ubiquitin in cell signaling. Mol Cell 33 275 286. 4. MukhopadhyayDRiezmanH 2007 Proteasome-independent functions of ubiquitin in endocytosis and signaling. Science 315 201 205. 5. LeeTVDingTChenZRajendranVScherrH 2008 The E1 ubiquitin-activating enzyme Uba1 in Drosophila controls apoptosis autonomously and tissue growth non-autonomously. Development 135 43 52. 6. DegterevAYuanJ 2008 Expansion and evolution of cell death programmes. Nat Rev Mol Cell Biol 9 378 390. 7. KumarS 2007 Caspase function in programmed cell death. Cell Death Differ 14 32 43. 8. BaoQShiY 2007 Apoptosome: a platform for the activation of initiator caspases. Cell Death Differ 14 56 65. 9. RiedlSJSalvesenGS 2007 The apoptosome: signalling platform of cell ...

The initiating events that lead to the induction of apoptosis mediated by the chemopreventative agent β-phenyethyl isothiocyanate (PEITC) have yet to be elucidated. In the present investigation, we examined the effects of PEITC on mitochondrial function and apoptotic signaling in hepatoma HepG2 cells and isolated rat hepatocyte mitochondria. PEITC induced a conformational change in Bax leading to its translocation to mitochondria in HepG2 cells. Bax accumulation was associated with a rapid loss of mitochondrial membrane potential (Δψm), impaired respiratory chain enzymatic activity, release of mitochondrial cytochrome c and the activation of caspase-dependent cell death. Caspase inhibition did not prevent Bax translocation, the release of cytochrome c or the loss of Δψ m, but blocked caspase-mediated DNA fragmentation and cell death. To determine whether PEITC dependent Bax translocation caused loss of Δψm by the activation of the mitochondrial permeability transition (MPT), we examined ...

Caspase 12 is a protein that belongs to a family of enzymes called caspases which cleave their substrates at C-terminal aspartic acid residues. It is closely related to caspase 1 and other members of the caspase family, known as inflammatory caspases, which process and activate inflammatory cytokines such as interleukin 1 and interleukin 18. It is found on chromosome 11 in humans in a locus with other inflammatory caspases. CASP12 orthologs have been identified in numerous mammals for which complete genome data are available. The CASP12 gene is subject to polymorphism, which can generate a full length caspase protein (Csp12L) or an inactive truncated form (Csp12S). The functional form appears to be confined to people of African descent and is linked with susceptibility to sepsis; people carrying the functional gene have decreased responses to bacterial molecules such as lipopolysaccharide (LPS). A study in May 2009 by McGill University Health Centre has suggested that estrogen may serve to block ...

The mammalian Golgi complex is comprised of a ribbon of stacked cisternal membranes often located in the pericentriolar region of the cell. Here, we report that during apoptosis the Golgi ribbon is fragmented into dispersed clusters of tubulo-vesicular membranes. We have found that fragmentation is caspase dependent and identified GRASP65 (Golgi reassembly and stacking protein of 65 kD) as a novel caspase substrate. GRASP65 is cleaved specifically by caspase-3 at conserved sites in its membrane distal COOH terminus at an early stage of the execution phase. Expression of a caspase-resistant form of GRASP65 partially preserved cisternal stacking and inhibited breakdown of the Golgi ribbon in apoptotic cells. Our results suggest that GRASP65 is an important structural component required for maintenance of Golgi apparatus integrity.

The caspase-3 (CPP32, apopain, YAMA) family of cysteinyl proteases has been implicated as key mediators of apoptosis in mammalian cells. Gelsolin was identified as a substrate for caspase-3 by screening the translation products of small complementary DNA pools for sensitivity to cleavage by caspase-3. Gelsolin was cleaved in vivo in a caspase-dependent manner in cells stimulated by Fas. Caspase-cleaved gelsolin severed actin filaments in vitro in a Ca2+-independent manner. Expression of the gelsolin cleavage product in multiple cell types caused the cells to round up, detach from the plate, and undergo nuclear fragmentation. Neutrophils isolated from mice lacking gelsolin had delayed onset of both blebbing and DNA fragmentation, following apoptosis induction, compared with wild-type neutrophils. Thus, cleaved gelsolin may be one physiological effector of morphologic change during apoptosis. ...

Death receptor (DR) ligation can lead to divergent signaling pathways causing either caspase-mediated cell death or cell proliferation and inflammation. These variations in cellular fate are determined by adaptor proteins that are recruited to the DR signaling complex. FLICE inhibitory protein (FLIP) is an established inhibitor of caspase-8-mediated apoptosis, and it is also involved in NF-kappa B

Zeng L., Li T., Xu D.C., Liu J., Mao G., Cui M.Z., Fu X., Xu X.. Cells undergo apoptosis through two major pathways, the extrinsic pathway (death receptor pathway) and the intrinsic pathway (the mitochondrial pathway). These two pathways can be linked by caspase-8-activated truncated Bid formation. Very recently, death receptor 6 (DR6) was shown to be involved in the neurodegeneration observed in Alzheimer disease. DR6, also known as TNFRSF21, is a relatively new member of the death receptor family, and it was found that DR6 induces apoptosis when it is overexpressed. However, how the death signal mediated by DR6 is transduced intracellularly is not known. To this end, we have examined the roles of caspases, apoptogenic mitochondrial factor cytochrome c, and the Bcl-2 family proteins in DR6-induced apoptosis. Our data demonstrated that Bax translocation is absolutely required for DR6-induced apoptosis. On the other hand, inhibition of caspase-8 and knockdown of Bid have no effect on DR6-induced ...

Apoptosis is a genetically programmed process for the elimination of damaged or redundant cells by activation of caspases (aspartate-specific cysteine proteases). The onset of apoptosis is controlled by numerous interrelating processes. The extrinsic pathway involves stimulation of members of the tumor necrosis factor (TNF) receptor subfamily, such as TNFRI, CD95/Fas or TRAILR (death receptors), located at the cell surface, by their specific ligands, such as TNF-alpha, FasL or TRAIL, respectively. The intrinsic pathway is activated mainly by non-receptor stimuli, such as DNA damage, ER stress, metabolic stress, UV radiation or growth-factor deprivation. The central event in the intrinsic pathway is the mitochondrial outer membrane permeabilization (MOMP), which leads to the release of cytochrome c. These two pathways converge at the level of effector caspases, such as caspase-3 and caspase-7. The third major pathway is initiated by the constituents of cytotoxic granules (e.g. Perforin and ...

Apoptosis is a genetically programmed process for the elimination of damaged or redundant cells by activation of caspases (aspartate-specific cysteine proteases). The onset of apoptosis is controlled by numerous interrelating processes. The extrinsic pathway involves stimulation of members of the tumor necrosis factor (TNF) receptor subfamily, such as TNFRI, CD95/Fas or TRAILR (death receptors), located at the cell surface, by their specific ligands, such as TNF-alpha, FasL or TRAIL, respectively. The intrinsic pathway is activated mainly by non-receptor stimuli, such as DNA damage, ER stress, metabolic stress, UV radiation or growth-factor deprivation. The central event in the intrinsic pathway is the mitochondrial outer membrane permeabilization (MOMP), which leads to the release of cytochrome c. These two pathways converge at the level of effector caspases, such as caspase-3 and caspase-7. The third major pathway is initiated by the constituents of cytotoxic granules (e.g. Perforin and ...

Apoptosis is a genetically programmed process for the elimination of damaged or redundant cells by activation of caspases (aspartate-specific cysteine proteases). The onset of apoptosis is controlled by numerous interrelating processes. The extrinsic pathway involves stimulation of members of the tumor necrosis factor (TNF) receptor subfamily, such as TNFRI, CD95/Fas or TRAILR (death receptors), located at the cell surface, by their specific ligands, such as TNF-alpha, FasL or TRAIL, respectively. The intrinsic pathway is activated mainly by non-receptor stimuli, such as DNA damage, ER stress, metabolic stress, UV radiation or growth-factor deprivation. The central event in the intrinsic pathway is the mitochondrial outer membrane permeabilization (MOMP), which leads to the release of cytochrome c. These two pathways converge at the level of effector caspases, such as caspase-3 and caspase-7. The third major pathway is initiated by the constituents of cytotoxic granules (e.g. Perforin and ...

Mon laboratoire sintéresse aux mécanismes dactivation, de régulation et dactivité des caspases, des enzymes importantes pour une multitude de processus biologiques et pathologiques. À long terme, notre objectif est délucider leur biologie afin de proposer des approches thérapeutiques nouvelles. Les caspases sont des enzymes très importantes pour linflammation, la mort cellulaire et plusieurs autres fonctions incluant diverses pathologies. Par exemple, certaines caspases ont une importance majeure dans les maladies neurodégénératives tel le Parkinson. Un des membres de cette famille, la caspase-7, joue un rôle lors de la mort cellulaire et durant un processus inflammatoire nouveau. Ce processus est important pour la destruction de certains pathogènes. Par conséquent, mon laboratoire sintéresse aux activateurs de la caspase-7, comment elle est contrôlée et comment elle agit sur ses cibles. De cette façon, notre laboratoire étudie plusieurs aspects de la biologie des ...

The robust and rapid induction of innate immune signaling is a hallmark of the host response to microbial infection. Successful pathogens subvert, thwart, or dismantle these defensive measures. Growing evidence suggests that the host recognizes these disruptive efforts, eliciting effective backup measures. Cell death processes, including apoptosis and pyroptosis, are integral components of the host response to infection. Multiprotein inflammasome complexes sense the presence of pathogens and activate inflammatory caspases, typically caspase-1 or caspase-11, leading to pyroptotic cell death and maturation of the inflammatory cytokines interleukin-1β (IL-1β) and IL-18. Pyroptosis is an inflammasome-driven cytotoxic process that occurs in macrophages after limited proteolysis of gasdermin D (GSDMD). The generation of an N-terminally cleaved fragment then creates large oligomeric membrane pores and causes lytic cell death (1-7). At present, caspase-1 and caspase-11 are the only known regulators of ...

This group of sequences represent the core of p45 (45 kDa) precursor of caspases, which can be processed to produce the active p20 (20 kDa) and p10 (10 kDa) subunits. Caspases (Cysteine-dependent ASPartyl-specific proteASE) are cysteine peptidases that belong to the MEROPS peptidase family C14 (caspase family, clan CD) based on the architecture of their catalytic dyad or triad [(PUBMED:11517925)]. Caspases are tightly regulated proteins that require zymogen activation to become active, and once active can be regulated by caspase inhibitors. Activated caspases act as cysteine proteases, using the sulphydryl group of a cysteine side chain for catalysing peptide bond cleavage at aspartyl residues in their substrates. The catalytic cysteine and histidine residues are on the p20 subunit after cleavage of the p45 precursor.. Caspases are mainly involved in mediating cell death (apoptosis) [(PUBMED:10578171), (PUBMED:10872455), (PUBMED:15077141)]. They have two main roles within the apoptosis cascade: ...

TY - JOUR. T1 - Reversibility of apoptosis in cancer cells. AU - Tang, H. L.. AU - Yuen, K. L.. AU - Tang, H. M.. AU - Fung, M. C.. PY - 2009/1/13. Y1 - 2009/1/13. N2 - Apoptosis is a cell suicide programme characterised by unique cellular events such as mitochondrial fragmentation and dysfunction, nuclear condensation, cytoplasmic shrinkage and activation of apoptotic protease caspases, and these serve as the noticeable apoptotic markers for the commitment of cell demise. Here, we show that, however, the characterised apoptotic dying cancer cells can regain their normal morphology and proliferate after removal of apoptotic inducers. In addition, we demonstrate that reversibility of apoptosis occurs in various cancer cell lines, and in different apoptotic stimuli. Our findings show that cancer cells can survive after initiation of apoptosis, thereby revealing an unexpected potential escape mechanism of cancer cells from chemotherapy.. AB - Apoptosis is a cell suicide programme characterised by ...

When cells kill themselves, they usually do so by activating mechanisms that have evolved specifically for that purpose. These mechanisms, which are broadly conserved throughout the metazoa, involve two processes: activation in the cytosol of latent cysteine proteases (termed caspases), and disruption of mitochondrial functions. These processes are linked in a number of different ways. While active caspases can cleave proteins in the mitochondrial outer membrane, and cleave and thereby activate certain pro-apoptotic members of the Bcl-2 family, proteins released from the mitochondria can trigger caspase activation and antagonise IAP family proteins. This review will focus on the pro-apoptotic molecules that are released from the mitochondria of cells endeavouring to kill themselves. This article is part of a Special Issue entitled Mitochondria: the deadly organelle ...

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When cells are infected, pathogen-derived proteins are processed by the proteasome, and the resultant peptides (after further processing) bind to the class I major histocompatibility complex (MHC) and are presented on the surface of the infected cell. CD8+ cytotoxic T lymphocytes (CTLs) recognize these peptide-MHC complexes and kill the infected cell. Noting that viral infection often activates caspases, cytosolic cysteine proteases that trigger apoptosis, López et al. investigated whether caspases might also contribute to antigen presentation. The authors infected murine cells with recombinant vaccinia virus (rVACV) that expressed a miniprotein (m19) and cultured the cells with CTL lines specific for an epitope within m19. The CTLs killed the infected cells and also killed infected cells that were incubated with either a proteasome-specific inhibitor or a caspase-specific inhibitor; however, treatment of the infected cells with both inhibitors blocked killing by the CTLs. Analysis of peptide ...

Caspases are normally suppressed by IAP (inhibitor of apoptosis) proteins (see Controlling the Caspases, by Stephen W. Fesik and Yigong Shi, in Science, Vol. 294, No. 5546, p. 1477, November 16, 2001). When a cell receives an apoptotic stimulus, IAP activity is relieved after SMAC (Second Mitochondria-derived Activator of Caspases, or its mouse homolog, called DIABLO), a mitochondrial protein, is reléased into the cytosol. SMAC binds to IAPs, and in doing so inhibits the inhibitors, effectively preventing them from arresting the apoptotic process. But before we go on to a short description of how SMAC is reléased, lets take a look at two well-studied extrinsically induced apoptotic processes: the TNF and the Fas pathways. Keep in mind, however, that both activating and inhibiting factors are present at éach step of these pathways. Tumor necrosis factor (TNF), a 157 amino acid inter-cellular signaling molecule (cytokine) produced mainly by activated macrophages, and is the major extrinsic ...

TY - JOUR. T1 - Caspases determine the vulnerability of oligodendrocytes in the ischemic brain. AU - Shibata, Mamoru. AU - Hisahara, Shin. AU - Hara, Hideaki. AU - Yamawaki, Takemori. AU - Fukuuchi, Yasuo. AU - Yuan, Junying. AU - Okano, Hideyuki. AU - Miura, Masayuki. PY - 2000/9. Y1 - 2000/9. N2 - Although oligodendrocytes (OLGs) are thought to be vulnerable to hypoxia and ischemia, little is known about the detailed mechanism by which these insults induce OLG death. From the clinical viewpoint, it is imperative to protect OLGs as well as neurons against ischemic injury (stroke), because they are the only myelin-forming cells of the central nervous system. Using the Cre/loxP system, we have established a transgenic mouse line that selectively expresses p35, a broad-spectrum caspase inhibitor, in OLGs. After hypoxia, cultured OLGs derived from wild-type mice exhibited significant upregulation of caspase-11 and substantial activation of caspase-3, which led to cell loss. Expression of p35 or ...

The present study examined levels of various components of the cell death machinery and drug sensitivity of 60 human cancer cell lines to anticancer drugs. With the exception of procaspase-3, which was undetectable in MCF-7 cells, caspases-2, -3, -6, -7, -8, and -9, as well as Apaf-1, were detectable in all 60 cell lines. Although these components of the cell death machinery varied widely in abundance, strong correlations between levels of Apaf-1 or procaspase-2, -3, -6, -8, or -9 and sensitivity to any class of antineoplastic agent were not observed. These results, although negative, have several important implications.. The attempt to correlate drug sensitivity with levels of various components of the cell death machinery was prompted by previous studies indicating that drug-induced apoptosis is markedly diminished when certain key components of the core cell-death machinery, particularly Apaf-1, procaspase-9, or procaspase-3, are genetically or functionally deleted (36, 37, 38 , 58 , 88 , 99) ...

Caspase-3 is a caspase protein that interacts with caspase-8 and caspase-9. It is encoded by the CASP3 gene. CASP3 orthologs have been identified in numerous mammals for which complete genome data are available. Unique orthologs are also present in birds, lizards, lissamphibians, and teleosts. The CASP3 protein is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes that undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein cleaves and activates caspases 6 and 7; and the protein itself is processed and activated by caspases 8, 9, and 10. It is the predominant caspase involved in the cleavage of amyloid-beta 4A precursor protein, which is associated with neuronal death in Alzheimers disease. Alternative splicing of this gene results in two ...

PTK787 2HCl and -7 (Lakhani et al. 2006 offers contributed to your knowledge of the physiological tasks of the caspases significantly. Oddly enough C57BL/6 mice deficient for both caspase-3 and -7 perish shortly after delivery while mice missing only caspase-3 or -7 have a normal life span and display a limited apoptotic phenotype in this genetic background (Lakhani et al. 2006 Leonard et al. 2002 This points to the functional redundancy between caspase-3 and -7 during embryogenesis. However several observations suggest that this overlap is not complete and that caspase-3 and -7 also fulfill non-redundant roles in apoptosis. For instance eye lenses of caspase-7 knockout mice are grossly normal whereas those of caspase-3 deficient mice display marked cataracts at the anterior lens pole (Zandy et al. 2005 Further support for this notion stems from biochemical studies demonstrating that caspase-3 and -7 exhibit differential activities toward multiple protein substrates with caspase-7 being more ...

Materials.Benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD-fmk), z-Asp-Glu-Val-Asp-fmk (zDEVD-fmk), boc-aspartyl(OMe)-fluoromethylketone (BAF), and the fluorogenic caspase substrate zDEVD-AFC were purchased from Enzyme Systems Products (Livermore, CA). Staurosporine was obtained from ICN Pharmaceuticals (Costa Mesa, CA). A cell lysis buffer for fluorogenic caspase activity assays was obtained from Clontech (ApoAlert CPP32 Assay Kit; Palo Alto, CA).. Cell culture. p53-deficient mice were generated from a 129/Sv × C57BL/6 background as described (Donehower et al., 1992). The genotypes of the mating pairs and all offspring were determined by PCR, using DNA extracted from the tail (Timme and Thompson, 1994). p53−/− mice were generated routinely from (+/−) × (−/−) mating pairs, whereas p53 wild-type mice were obtained by crossing p53+/+ mice. The brains from individual animals were cultured separately and genotyped before treatment.. Neuronal cultures derived from embryonic day ...

Caspases are important players in programmed cell death. Normal activities of caspases are critical for the cell life cycle and dysfunction of caspases may lead to the development of cancer and neurodegenerative diseases. They have become a popular target for drug design against abnormal cell death. In this study, the recognition of P5 position in substrates by caspase-3, -6 and -7 has been investigated by kinetics, modeling and crystallography. Crystal structures of caspase-3 and -7 in complexes with substrate analog inhibitor Ac-LDESD-CHO have been determined at resolutions of 1.61 and 2.45 Å, respectively, while a model of caspase-6/LDESD is constructed. Enzymatic study and structural analysis have revealed that Caspase-3 and -6 recognize P5 in pentapeptides, while caspase-7 lacks P5-binding residues. D-arginine dehydrogenase catalyzes the flavin-dependent oxidative deamination of D-amino acids to the corresponding imino acids and ammonia. The X-ray crystal structures of DADH and its complexes with

BioAssay record AID 666968 submitted by ChEMBL: Inhibition of human recombinant caspase-3 catalytic domain using Ac-DEVD-pNA as substrate at 20 ug/ml preincubated for 30 mins before substrate addition measured after 3 mins.

Caspase-1, originally called ICE, was the first mammalian analogue of the Caenorhabditis elegans death genes to be identified.11 Like all caspases, it is expressed as a proform, which is activated through proteolytic cleavage of an amino-terminal 11-kDa prodomain to release p20 and p10 subunits. Active caspase-1/ICE consists of a (p20/p10)2 tetramer, which is sufficient to process precursor IL-1β9,12-14 and, in at least some cell types, to induce apoptosis.16 Additionally, the prodomain has been postulated to have independent proapoptotic activity by enhancing death receptor-mediated caspase-8 activation.39 Although caspase-1 has conventionally been regarded as a proinflammatory, not a proapoptotic, caspase,10-12 it has been observed to induce or amplify apoptosis in tissue culture models.15,16. Regulated expression of caspase-1 in cardiac hypertrophy,17 the dilated cardiomyopathy of TNF-α overexpression,19 ischemia/infarction,21 and endotoxin-induced myocardial dysfunction18 prompted our ...

The mode of cell death during galactosamine (Gal)-induced liver injury was originally thought to be oncotic necrosis but recently it was suggested to be apoptosis. Thus, the objective was to assess whether apoptosis and oncosis are sequential or independent events in the pathophysiology. In addition, the role of caspases in Gal-induced apoptotic signaling was investigated. A dose of 500 mg/kg Gal caused a time-dependent increase in plasma alanine transaminase (ALT) levels (24 h: 430 ± 122 U/L) in female Sprague-Dawley rats. This was accompanied by processing of procaspase-3 and significant increases in hepatic and plasma caspase-3 activities. Using morphology and TUNEL staining, apoptotic and oncotic cells were quantitated. The number of apoptotic hepatocytes increased from 0.14% in controls to 5.4 ± 1.0% 24 h after Gal treatment. In addition, the number of cells with oncotic morphology increased from 0 to 6.9% of total hepatocytes. Treatment with the pan-caspase inhibitor IDN-7314 (10 mg/kg) or

PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Kathleen Godfrey - President , Godfrey Financial Associates, Inc. When a Last Will and Testament is drafted, one of the most important considerations is the naming of an Executor or Executrix. Presumably, the Executor or Executrix is well-known by the decedent. However, this person often has little knowledge of their responsibilities. While not an exhaustive list, below are 10 important responsibilities of an Executor or Executrix.. 1. First Steps. ...

MALT1 reglerar medfödd immunitet men hur detta sker är fortfarande oklara. Vi använde den selektiva MALT1 paracaspase hämmaren MLT-827...

The activation of microglia, resident immune cells of the central nervous system, and inflammation-mediated neurotoxicity are typical features of neurodegenerative diseases, for example, Alzheimers and Parkinsons diseases. An unexpected role of caspase-3, commonly known to have executioner role for apoptosis, was uncovered in the microglia activation process. A central question emerging from this finding is what prevents caspase-3 during the microglia activation from killing those cells? Caspase-3 activation occurs as a two-step process, where the zymogen is first cleaved by upstream caspases, such as caspase-8, to form intermediate, yet still active, p19/p12 complex; thereafter, autocatalytic processing generates the fully mature p17/p12 form of the enzyme. Here, we show that the induction of cellular inhibitor of apoptosis protein 2 (cIAP2) expression upon microglia activation prevents the conversion of caspase-3 p19 subunit to p17 subunit and is responsible for restraining caspase-3 in ...

This study investigated the possible involvement of a specific caspase(s) (a family of aspartate-specific cysteine proteases) in programmed cell death of islet beta-cells due to sustained GTP depletion. Treatment (up to 48 h) with 3 microg/ml mycophenolic acid (MPA), which specifically depletes intr …

Commentary 2801 Introduction Apoptosis is essential for normal development and tissue homeostasis, and perturbations in its regulation contribute to numerous pathological conditions, including cancer and autoimmune and degenerative diseases (Adams and Cory, 2007; Meier and Vousden, 2007). There are two main pathways that lead to apoptosis: the extrinsic pathway, which is triggered following the activation of cell-surface-expressed death receptors such as CD95 (also known as Fas receptor) and tumour necrosis factor receptor; and the intrinsic pathway, which is activated by cellular stress and is regulated primarily at the level of mitochondria by the Bcl-2 family of proteins (Fig. 1). The intrinsic apoptotic pathway is initiated in response to a variety of stress signals (Willis and Adams, 2005), and a complex interplay of Bcl-2 proteins relays this signal to the mitochondrial outer membrane (OM) to initiate Bak and Bax activation, oligomerisation and OM damage (Fig. 1). Breaching the ...

Actually, that is a very long story; we worked on that one for some time. We started working on it because of our interest in TNF. Certain cells, when treated with TNF, undergo necrotic cell death. The molecular basis of necrosis is poorly defined right now, but the most practical definition for our study is that it is a form of cell death that, unlike apoptosis, does not involve caspases. We wanted to see if we could find a key molecule that is important for necrosis.. We had been working on this problem for a while when I heard about a paper that another group had published, which claimed that TNF-treated NIH-3T3 cells didnt undergo apoptotic cell death, because if you blocked caspases, the cells would still die. I thought this was interesting because, generally speaking and also in our hands, TNF treatment of NIH-3T3 cells causes apoptosis, and does involve caspases. So we got some of these necrotic NIH-3T3 cells, and we compared their gene expression profile to our apoptotic NIH-3T3 cell ...

PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

The NucView® caspase-3 substrates are activity-dependent i.e. require active caspase-3 enzyme. In dead, fixed and preserved cells or tissue sections, there are no active caspases and hence these substrates cannot be used. We also offer TUNEL assay kits that are suitable for apoptosis detection in fixed cells and tissues. The kits employ dUTPs conjugated to our exceptionally bright and photostable CF® dyes for single-step fluorescent TUNEL labeling of DNA strand breaks, a hallmark of apoptotic cells, and are suitable for analysis by fluorescence microscopy or flow cytometry.. ...

The response of psoriasis to antibodies targeting the interleukin (IL)-23/IL-17A pathway suggests a prominent role of T-helper type-17 (Th17) cells in this disease. had not been detectable in neutrophils isolated from VX-950 dynamic plaques. Significant medical reactions to secukinumab had been noticed 2?weeks following a solitary infusion, connected with extensive clearance of cutaneous neutrophils parallel towards the normalization of keratinocyte abnormalities and reduced amount of IL-17-inducible neutrophil chemoattractants (e.g. (TNF-(monoclonal antibody selective for IL-17A, or placebo inside a 3:3:3:1 percentage (information regarding test size computation, randomization and blinding are given within the Assisting Information). There have been low- and middle- single-dose cohorts who received secukinumab 3 and 10?mg/kg, respectively, infused on Day time 1 (with placebo administered on Day time 15 and Day time 29) along with a high-dose cohort who have received 3 infusions of secukinumab ...

Supplementary MaterialsDataSheet_1. the additional four baseline strategies. Furthermore, we validated the predictions from the MDADTI in six drug-target connections reference databases, as well as the outcomes demonstrated that MDADTI can identify unknown DTIs effectively. = 1,……,? and a couple of goals T?= = 1,……,, where represents the real variety of medications and represents the amount of goals. We also described the connections between D and T being a binary matrix Y whose component beliefs are 0 or 1, where = 1 represents the medication and similarity matrices of goals in = to get the topology framework feature of medication nodes. The RWR strategy can be developed as the next recurrence relationship: is normally a row vector of medication and its techniques starting from 99011-02-6 medication may be the preliminary one-hot vector, is the probability of restart, and is the one-step probability transition matrix acquired by applying row-wise normalization of the similarity matrix ...

In Figure 3, they added the DRACOs to these cells, either with, or without the inhibitor. They also included a product which makes cells which have just self destructed glow in the dark. The first four sections on the graph are simply controls, to pick up the background levels of cell death. Since the main function of caspases is to cause cell death to occur, you can guess what would happen if we were to add caspase inhibitors to a normal set of cells. The blue and red bars are both lower than the green bar , because they have the caspase inhibitors added. The next three sections show what happens when DRACOs are added to the mix, and they show that they kill off a lot of cells. And importantly, you can tell that its performed using caspases, because in the presence of inhibitor, the cells do not die as much. In fact, the levels of death seen is more or less the same as the other controls with inhibitors ...

Apoptosis is a distinct form of cell death that is functionally and morphologically different from necrosis. Nuclear chromatin condensation, cytoplasmic shrinking, dilated endoplasmic reticulum, and membrane blebbing characterize apoptosis in general. Mitochondria remain morphologically unchanged. In 1972 Kerr et al introduced the concept of apoptosis as a distinct form of cell-death, and the mechanisms of various apoptotic pathways are still being revealed today. Proteins on this pathway have targeted assays available via the CPTAC Assay Portal ...

Apoptosis is a distinct form of cell death that is functionally and morphologically different from necrosis. Nuclear chromatin condensation, cytoplasmic shrinking, dilated endoplasmic reticulum, and membrane blebbing characterize apoptosis in general. Mitochondria remain morphologically unchanged. In 1972 Kerr et al introduced the concept of apoptosis as a distinct form of cell-death, and the mechanisms of various apoptotic pathways are still being revealed today ...

In Situ Pan-Caspase Assay Kit from CHEMICON,Apoptosis is an evolutionarily conserved form of cell suicide, which follows a specialized cellular process. The central component of this process is a cascade of proteolytic enzymes called caspases. These enzymes participate in a series of reactions that are triggered in response to pro-apoptoti,biological,biology supply,biology supplies,biology product