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BAG-1 has been identified as a Bcl-2-binding protein that inhibits apoptosis, either alone or in co-operation with Bcl-2. Here we show that BAG-1 inhibits p53- induced apoptosis in the human tumour cell line Saos-2. In contrast, BAG-1 was unable to inhibit the p53-independent pathway induced by apoptin, an apoptosis-inducing protein derived from chicken anaemia virus. Whereas BAG-1 seemed to co-operate...
DNase γ, which cleaves chromosomal DNA into nucleosomal units (DNA ladder formation), has been suggested to be the critical component of apoptotic machinery. Using rat pheochromocytoma PC12 cells, which are differentiated to sympathetic neurons by nerve growth factor (NGF), we investigated whether DNase γ-like enzyme is present in neuronal cells and is involved in neuronal cell death. The nuclear...
Alterations in intracellular free calciumconcentration ([Ca2+]i) areinstrumental in apoptosis. We have previously shown that a[Ca2+]i increase above 1000 nM isrelated to the appearance of apoptosis in serum-free cultures ofgranulosa cell sheets. In the present study we examined how the[Ca2+]i increase relates toindicators of distinct phases of the apoptotic cascade. We used adouble staining technique...
The importance of caspases in developmental neuronal death is well-established. Recent data provide compelling evidence of caspase activation after ischaemic brain injury. Caspase inhibitors reduce cell death in several models of ischaemic injury. This review summarizes our current understanding of caspase function in ischaemic brain injury and examines the accumulating evidence of caspase participation...
Survival factors activate kinases which, in turn, phosphorylate the proapoptotic Bcl-xl/Bcl-2-associated death promoter homolog (BAD) protein at key serine residues. Phosphorylated BAD interacts with 14-3-3 proteins, and overexpression of 14-3-3 attenuates BAD-mediated apoptosis. Although BAD is known to interact with Bcl-2, Bcl-w, and Bcl-xL, the exact relationship between BAD and anti- or proapoptotic...
Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases, which can synergistically degrade the major components of extracellular matrix (ECM). A key role in maintaining the balance between ECM deposition and degradation in several physio-pathological processes is carried out, through multiple biological functions, by four members of the tissue inhibitors of metalloproteinases...
Adult skeletal muscle has the striking ability to repair and regenerate itself after injury. This would not be possible without satellite cells, a subpopulation of cells existing at the margin of the myofiber. Under most conditions, satellite cells are quiescent, but they are activated in response to trauma, enabling them to guide skeletal muscle regeneration. In degenerative skeletal muscle states,...
Background: HSV fulminant hepatitis is a rare pathology. Rapid hepatic failure, as a consequence of extended liver damage, has generally been attributed to necrosis. As apoptosis can constitute another way for hepatocytes to die, we decided to investigate whether programmed cell death took place during HSV fulminant hepatitis. Methods: Liver sections were obtained from two cases of fulminant herpetic...
Apoptosis is characterized by chromatin condensation, DNA cleavage, redistribution of phosphatidylserine, and apoptotic body formation via an actin-dependent process. We describe a novel form of the execution phase of apoptosis in human multiple myeloma cells that is morphologically and mechanistically distinct from classical apoptosis, but is caspase-dependent and inhibited by IL-6 and overexpression...
Cytomegaloviruses (CMVs), a subset of betaherpesviruses, employ multiple strategies to suppress apoptosis in infected cells and thus to delay their death. Human cytomegalovirus (HCMV) encodes at least two proteins that directly interfere with the apoptotic signaling pathways, viral inhibitor of caspase-8-induced apoptosis vICA (pUL36), and mitochondria-localized inhibitor of apoptosis vMIA (pUL37...
An increasing number of reports indicate that single-celled organisms are able to die following what seems to be an ordered program of cell death with strong similarities to apoptosis from higher eukaryotes. DNA degradation and several other apoptotic-like processes have also been described in the parasitic protozoa Leishmania. However, the existence of an apoptotic death in this parasite is still...
HAMLET (Human α-lactalbumin Made Lethal to Tumor cells) triggers selective tumor cell death in vitro and limits tumor progression in vivo. Dying cells show features of apoptosis but it is not clear if the apoptotic response explains tumor cell death. This study examined the contribution of apoptosis to cell death in response to HAMLET. Apoptotic changes like caspase activation, phosphatidyl serine...
Developing neuronal populations undergo significant attrition by natural cell death. Dopaminergic neurons in the substantia nigra pars compacta undergo apoptosis during synaptogenesis. Following this time window, destruction of the anatomic target of dopaminergic neurons results in dopaminergic cell death but the morphology is no longer apoptotic. We describe ultrastructural changes that appear unique...
Here we show a detailed analysis of cellular and molecular events during in vivo apoptotic cell death in the INZs (interdigital necrotic zones) of the embryonic limb. As the apoptotic mechanisms proceed, the transcriptionally active chromatin and nuclear traffic of RNAs are disrupted, cytoskeletal components are disorganized and the adhesive properties of cells are compromised as Paxillin, a clue...
Programmed cell death (PCD) occurs in animals and plants under various stresses and during development. Recently, vacuolar processing enzyme (VPE) was identified as an executioner of plant PCD. VPE is a cysteine protease that cleaves a peptide bond at the C-terminal side of asparagine and aspartic acid. VPE exhibited enzymatic properties similar to that of a caspase, which is a cysteine protease that...
Intervertebral disc (IVD) degeneration is largely a process of destruction and failure of the extracellular matrix (ECM), and symptomatic IVD degeneration is thought to be one of the leading causes of morbidity or life quality deterioration in the elderly. To date, however, the mechanism of IVD degeneration is still not fully understood. Cellular loss from cell death in the process of IVD degeneration...
The systemic pathophysiologic changes following thermal injuries affect multiple organs and body systems leading to clinical manifestations including shock, intestinal alterations, respiratory and renal failure, immunosuppression and others. Recent advances in the comprehension of mechanisms underlying systemic complications of thermal injuries have contributed to uncover part of the cellular and...
Mitochondria are not only important for the energetic status of the cell, but are also the fatal organelles deciding about cellular life and death. Complex mitochondrial features decisive for cell death execution in mammals are present and functional in yeast: AIF and cytochrome c release to the cytosol, mitochondrial fragmentation as well as mitochondrial hyperpolarisation followed by an oxidative...
Programmed cell death can be divided into apoptosis and autophagic cell death. We describe the biological activities of TMEM166 (transmembrane protein 166, also known as FLJ13391), which is a novel lysosome and endoplasmic reticulum-associated membrane protein containing a putative TM domain. Overexpression of TMEM166 markedly inhibited colony formation in HeLa cells. Simultaneously, typical morphological...
One hallmark of programmed cell death (PCD) is redistribution of phosphatidylserine (PS) to the plasma membrane’s outer leaflet. Annexin V is widely used in cell death research due to its calcium-dependent ability to bind phosphatidylserine, thus marking apoptotic cells. However, calcium is invariably used at high concentrations in annexin V staining, at doses that can induce cell death. We used flow...
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