Search results for "calpain"
showing 10 items of 29 documents
CALPAIN ACTIVITY MAINTAINS GOOD HEALTH OF CENTENARIAN T CELLS; SUMMARY OF THE CALPACENT PROJECT
2017
Causes of aging-associated deterioration of human immunity, and the reasons why the immune system of the oldest old individuals (centenarians) is relatively robust, remain moot. Intracellular proteolysis system of two proteases – µ- and m-calpain – and their inhibitor – calpastatin (the calpain-calpastatin system (CCS)) - is active in resting human peripheral blood T cells, participating in maintenance of their readiness to proliferate and secrete cytokines in response to stimulation. The amounts of the CCS proteins decrease in resting T lymphocytes of healthy elderly, only to return in the centenarians to those levels seen in the young individuals. We compared the calpain activities and th…
Selective uptake and degradation of c-Fos and v-Fos by rat liver lysosomes
1996
AbstractThe transcription factor c-Fos is a short-lived protein and calpains and ubiquitin-dependent systems have been proposed to be involved in its degradation. In this report, we consider a lysosomal degradation pathway for c-Fos. Using a cell-free assay, we have found that freshly isolated lysosomes can take up and degrade c-Fos with high efficiency. v-Fos, the oncogenic counterpart of c-Fos, can also be taken up by lysosomes, yet the amount of incorporated protein is much lower. c-Fos uptake is independent of its phosphorylation state but it appears to be regulated by dimerization with differentially phosphorylated forms of c-Jun, while v-Fos escapes this regulation. Moreover, we show …
Differential functions of calpain 1 during epithelial cell death and adipocyte differentiation in mammary gland involution
2014
Calpains become activated in the mammary gland early during weaning, cleaving several proteins located mainly in the cell membrane, but also in other organelles such as lysosomes, mitochondria and nuclei. By immunofluorescence and Western blot analysis, we have demonstrated the nuclear translocation of calpain-1 and calpain-2, together with the cleavage of several cytoplasmic nucleoporins in epithelial cells of the lobulo-alveolar compartment. In vivo and in vitro calpain inhibition prevented this nucleoporin degradation. In addition, calpain-1 was also present in the nucleus of non-epithelial mammary tissue cells, concomitant with adipocyte re-differentiation. Calpain-1 was internalized wi…
Involvement of cyclin-dependent kinase-5 in the kainic acid-mediated degeneration of glutamatergic synapses in the rat hippocampus.
2011
Increased levels of glutamate causing excitotoxic damage accompany neurological disorders such as ischemia/stroke, epilepsy and some neurodegenerative diseases. Cyclin-dependent kinase-5 (Cdk5) is important for synaptic plasticity and is deregulated in neurodegenerative diseases. However, the mechanisms by which kainic acid (KA)-induced excitotoxic damage involves Cdk5 in neuronal injury are not fully understood. In this work, we have thus studied involvement of Cdk5 in the KA-mediated degeneration of glutamatergic synapses in the rat hippocampus. KA induced degeneration of mossy fiber synapses and decreased glutamate receptor (GluR)6/7 and post-synaptic density protein 95 (PSD95) levels in…
Androglobin: a chimeric globin in metazoans that is preferentially expressed in mammalian testes
2012
Abstract: Comparative genomic studies have led to the recent identification of several novel globin types in the Metazoa. They have revealed a surprising evolutionary diversity of functions beyond the familiar O2 supply roles of hemoglobin and myoglobin. Here we report the discovery of a hitherto unrecognized family of proteins with a unique modular architecture, possessing an N-terminal calpain-like domain, an internal, circular permuted globin domain, and an IQ calmodulin-binding motif. Putative orthologs are present in the genomes of many metazoan taxa, including vertebrates. The calpain-like region is homologous to the catalytic domain II of the large subunit of human calpain-7. The glo…
The molecular basis of filamin binding to integrins and competition with talin.
2006
The ability of adhesion receptors to transmit biochemical signals and mechanical force across cell membranes depends on interactions with the actin cytoskeleton. Filamins are large, actin-crosslinking proteins that connect multiple transmembrane and signaling proteins to the cytoskeleton. Here, we describe the high-resolution structure of an interface between filamin A and an integrin adhesion receptor. When bound, the integrin beta cytoplasmic tail forms an extended beta strand that interacts with beta strands C and D of the filamin immunoglobulin-like domain (IgFLN) 21. This interface is common to many integrins, and we suggest it is a prototype for other IgFLN domain interactions. Notabl…
Calpains mediate epithelial-cell death during mammary gland involution: mitochondria and lysosomal destabilization.
2012
Our aim was to elucidate the physiological role of calpains (CAPN) in mammary gland involution. Both CAPN-1 and -2 were induced after weaning and its activity increased in isolated mitochondria and lysosomes. CAPN activation within the mitochondria could trigger the release of cytochrome c and other pro-apoptotic factors, whereas in lysosomes it might be essential for tissue remodeling by releasing cathepsins into the cytosol. Immunohistochemical analysis localized CAPNs mainly at the luminal side of alveoli. During weaning, CAPNs translocate to the lysosomes processing membrane proteins. To identify these substrates, lysosomal fractions were treated with recombinant CAPN and cleaved produc…
Targeting the mitochondrial pathway to induce apoptosis/necrosis through ROS by a newly developed Schiff’s base to overcome MDR in cancer
2011
Abstract Multidrug resistance (MDR) in cancer, a major obstacle to successful application of cancer chemotherapy, is often characterized by over-expression of multidrug resistance-related proteins such as MRP1, P-gp or elevated glutathione (GSH) level. Efflux of drugs by functional P-gp, MRP1 and elevated GSH level can confer resistance to apoptosis induced by a range of different stimuli. Therefore, it is necessary to develop new cell death inducers with relatively lower toxicity toward non-malignant cells that can overcome MDR by induction of apoptotic or non-apoptotic cell death pathways. Herein we report the synthesis and spectroscopic characterization of a GSH depleting, redox active S…
µ-Calpain conversion of antiapoptotic Bfl-1 (BCL2A1) into a prodeath factor reveals two distinct alpha-helices inducing mitochondria-mediated apoptos…
2011
Anti-apoptotic Bfl-1 and pro-apoptotic Bax, two members of the Bcl-2 family sharing a similar structural fold, are classically viewed as antagonist regulators of apoptosis. However, both proteins were reported to be death inducers following cleavage by the cysteine protease µ-calpain. Here we demonstrate that calpain-mediated cleavage of full-length Bfl-1 induces the release of C-terminal membrane active α-helices that are responsible for its conversion into a pro-apoptotic factor. A careful comparison of the different membrane-active regions present in the Bfl-1 truncated fragments with homologous domains of Bax show that helix α5, but not α6, of Bfl-1 induces cell death and cytochrome c r…
Calpain 1 and 2 Are Required for RNA Replication of Echovirus 1▿
2007
ABSTRACT Calpains are calcium-dependent cysteine proteases that degrade cytoskeletal and cytoplasmic proteins. We have studied the role of calpains in the life cycle of human echovirus 1 (EV1). The calpain inhibitors, including calpeptin, calpain inhibitor 1, and calpain inhibitor 2 as well as calpain 1 and calpain 2 short interfering RNAs, completely blocked EV1 infection in the host cells. The effect of the inhibitors was not specific for EV1, because they also inhibited infection by other picornaviruses, namely, human parechovirus 1 and coxsackievirus B3. The importance of the calpains in EV1 infection also was supported by the fact that EV1 increased calpain activity 3 h postinfection. …