Cell Death (Total 2883912 Papers Found)

Ataxia telangiectasia-mutated and Rad3-related (ATR) plays a central role in cell-cycle regulation, transmitting DNA damage signals to downstream effectors of cell-cycle progression. In animals, ATR is an essential gene. Here, we find that Arabidopsis (Arabidopsis thaliana) atr-/- mutants were viable, fertile, and phenotypically wild-type in the absence of exogenous DNA damaging agents but exhibit altered expression of AtRNR1 (ribonucleotide reductase large subunit) and alteration of some damage ...
A structure of the Escherichia coli chromosomal MazE/MazF addiction module has been determined at 1.7 A resolution. Addiction modules consist of stable toxin and unstable antidote proteins that govern bacterial cell death. MazE (antidote) and MazF (toxin) form a linear heterohexamer composed of alternating toxin and antidote homodimers (MazF(2)-MazE(2)-MazF(2)). The MazE homodimer contains a beta barrel from which two extended C termini project, making interactions with flanking MazF homodimers ...
Autophagy is characterized by the sequestration of bulk cytoplasm, including damaged proteins and organelles, and delivery of the cargo to lysosomes for degradation. Although the autophagic pathway is also linked to tumour suppression activity, the mechanism is not yet clear. Here we report that cytosolic FoxO1, a forkhead O family protein, is a mediator of autophagy. Endogenous FoxO1 was required for autophagy in human cancer cell lines in response to oxidative stress or serum starvation, but t ...
Bortezomib, a proteasome inhibitor, shows substantial anti-tumor activity in a variety of tumor cell lines, is in phase I, II, and III clinical trials and has recently been approved for the treatment of patients with multiple myeloma. The sequence of events leading to apoptosis following proteasome inhibition by bortezomib is unclear. Bortezomib effects on components of the mitochondrial apoptotic pathway were examined: generation of reactive oxygen species (ROS), alteration in the mitochondrial ...
Human type 1 diabetes results from the selective destruction of insulin-producing pancreatic beta cells during islet inflammation. Cytokines and reactive radicals released during this process contribute to beta-cell death. Here we show that mice with a disrupted gene coding for poly (ADP-ribose) polymerase (PARP–/– mice) are completely resistant to the development of diabetes induced by the beta-cell toxin streptozocin. The mice remained normoglycemic and maintained normal levels of total pa ...
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by polyglutamine expansion in the disease protein, huntingtin. In HD patients and transgenic mice, the affected neurons form characteristic ubiquitin-positive nuclear inclusions (NIs). We have established ecdysone-inducible stable mouse Neuro2a cell lines that express truncated N-terminal huntingtin (tNhtt) with different polyglutamine lengths which form both cytoplasmic and nuclear aggregates in a polyglutamine ...
Our previous studies have shown that the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) prevents neuronal cell death caused by several neurotoxins. The present study sought to determine the neuroprotective effect of EGCG when it is administered after the induction of cell damage ('neurorescue'). In an attempt to imitate a progressive mode of death, PC12 cells were initially subjected to serum-starvation conditions for a period of 1 or 3 days before administration of EGCG (0.1-10 micr ...
The distribution and density of pituitary adenylate cyclase-activating polypeptide (PACAP) binding sites have been investigated in the brain of the primates Jacchus callithrix (marmoset) and Macaca fascicularis (macaque) using [(125)I]-PACAP27 as a radioligand. PACAP binding sites were widely expressed in the brain of these two species with particularly high densities in the septum, hypothalamus and habenula. A moderate density of recognition sites was seen in all subdivisions of the cerebral co ...
Hepatitis B Virus (HBV) infection is one of the major causes of hepatocellular carcinoma (HCC). X protein (HBx) has been suspected to be oncogenic, although the precise role(s) remain uncertain. HBx is a multifunctional viral regulator that modulates transcription, cell responses to genotoxic stress, protein degradation, and signaling pathways. These modulations affect viral replication and viral proliferation, directly or indirectly. HBx also affects cell cycle checkpoints, cell death, and carc ...
Oxidative stress, the result of cellular production of reactive oxygen species (ROS), has been implicated in a number of diseases of the eye. Exposure of eye tissues (e.g. the cornea and retina) to oxidative stress over time has been hypothesized to underlie the development of age-related macular degeneration (AMD) and maturity onset cataract formation. Light-induced free radicals can damage the eye, and alterations in the antioxidant defenses of the eye have been suggested to play a role in the ...
Thermal injury-associated specific immune deficiency occurs despite indicators of systemic activation of the lymphoid compartment. We investigated the possibility that postburn immune failure and T cell activation are causally related through activation-induced (apoptotic) cell death. The relationship between the cellular immune response and cell mortality was examined in cultures of peripheral blood mononuclear cells (PBMC) from 14 immunosuppressed patients with extensive burns (35–90% total ...
It was recently demonstrated that renal tissue transglutaminase (tTg) protein and its catalytic product the epsilon(gamma-glutamyl) lysine protein cross-link are significantly increased in the subtotal (5/6) nephrectomy model (SNx) of renal fibrosis in rats. It was proposed that the enzyme had two important physiologic functions in disease development; one of stabilizing the increased extracellular matrix (ECM) by protein cross-linking, the other in a novel form of tubular cell death. This study ...
Manganese is an essential nutrient for humans that has to be maintained at proper levels for normal brain functioning. However, manganese also acts as a toxicant to the brain, and several studies have linked exposure to excessive manganese to neurotoxicity in adults. A recent report has suggested that ingesting high doses of manganese via drinking water can impede intellectual functions in children. It is known that during development, the nervous system is particularly vulnerable to different t ...
The aim of this study was to investigate the role of diffusion imaging in the evaluation of response to neoadjuvant breast cancer treatment by correlating apparent diffusion coefficient (ADC) value changes with pathological response. From June 2007 to June 2009, all consecutive patients with histopathologically confirmed breast cancer undergoing neoadjuvant chemotherapy were enrolled. All patients underwent magnetic resonance imaging (MRI) (including diffusion sequence) before and after neoadjuv ...
The NOD-like receptor (NLR) family of proteins is involved in the regulation of innate immune responses and cell death pathways. Recent findings show that the NLR family member NLRC4 (also known as IPAF) has important roles in innate immune responses to Gram-negative bacteria. Macrophages infected with Legionella pneumophila, Salmonella typhimurium, Shigella flexneri, or Pseudomonas aeruginosa activate caspase-1 in an NLRC4-dependent manner leading to macrophage cell death and the release of pro ...
Stem cells have been identified as a source of virtually all highly differentiated cells that are replenished during the lifetime of an animal. The critical balance between stem and differentiated cell populations is crucial for the long-term maintenance of functional tissue types. Stem cells maintain this balance by choosing one of several alternate fates: self-renewal, commitment to differentiate, and senescence or cell death. These characteristics comprise the core criteria by which these cel ...
Cisplatin is an antineoplastic drug, mostly documented to cause cell death through the formation of DNA adducts. In patients, it exhibits a range of short-term side effects that are unlikely to be related to its genomic action. As cisplatin has been shown to modify membrane properties in different cell systems, we investigated its effects on mechanosensitive ion transporters and channels. We show here that cisplatin is a noncompetitive inhibitor of the mechanosensitive Na(+)/H(+) exchanger NHE-1 ...
The effect of the photoproducts of indole-3-acetic acid sensitized by riboflavin on nonirradiated human HL-60 and murine NSO/2 tumor cells was studied. Severe damage with a dose-response effect was observed on both cell types. The effect was greater than that previously described for the tryptophan riboflavin photoproducts. Electron microscopy studies and flow cytometry analysis of DNA fragmentation allowed us to conclude that the photoproducts studied in this work induce cell death by an apopto ...
Proteases are now firmly established as major regulators of the "execution" phase of apoptosis. Here, we examine the role of proteases and their relationship to ceramide, a proposed mediator of apoptosis, in the tumor necrosis factor-alpha (TNF-alpha)-induced pathway of cell death. Ceramide induced activation of prICE, the protease that cleaves the death substrate poly(ADP-ribose) polymerase. Bcl-2 inhibited ceramide-induced death, but not ceramide generation. In contrast, Cytokine response modi ...
Recent genetic studies have revealed that some patients with primary cardiomyopathy (CM) possess mutations in the mitochondrial (mt) DNA of the myocardium (mtCM). Somatically acquired mutations such as deletions in mtDNA are caused mainly by hydroxyl radical damage to mtDNA. Cumulative accumulation of these somatic mutations during the life of an individual causes a bioenergetic deficit leading to myocardial dysfunction and cell death. The base-sequencing of the entire mtDNA from 48 individuals ...
Malignant glioma cells are generally resistant or only weakly sensitive to tumor necrosis factor family of cell death-inducing ligands, including TNF-related apoptosis-inducing ligand (TRAIL)/Apo2L. The chemopreventive activity of polyphenolic compounds present in plant-derived food products has been well recognized in epidemiological studies; however, the mechanism of chemoprevention by these dietary constituents largely remains unknown. Curcumin, the yellow pigment in the spice turmeric, has p ...
Singlet oxygen is a highly reactive form of molecular oxygen that may harm living systems by oxidizing critical cellular macromolecules and it also promotes deleterious processes such as cell death. Recently, we demonstrated that the control of redox balance and the cellular defense against oxidative damage are the primary functions of cytosolic NADP+-dependent isocitrate dehydrogenase (IDPc) through supplying NADPH for antioxidant systems. In this report, we demonstrate that modulation of IDPc ...
Apoptosis plays an important role in the pathogenesis of many viral infections. Despite this fact, the apoptotic pathways triggered during viral infections are incompletely understood. We now provide the first detailed characterization of the pattern of caspase activation following infection with a cytoplasmically replicating RNA virus. Reovirus infection of HEK293 cells results in the activation of caspase-8 followed by cleavage of the pro-apoptotic protein Bid. This initiates the activation of ...
Cells dying by necrosis release the high-mobility group box 1 (HMGB1) protein, which has immunostimulatory effects. However, little is known about the direct actions of extracellular HMGB1 protein on cancer cells. Here, we show that recombinant human HMGB1 (rhHMGB1) exerts strong cytotoxic effects on malignant tumor cells. The rhHMGB1-induced cytotoxicity depends on the presence of mitochondria and leads to fast depletion of mitochondrial DNA, severe damage of the mitochondrial proteome by toxic ...
Apoptosis is a term used to describe certain forms of physiological cell death that occur during embryogenesis, differentiation, and normal cell turnover. Previous reports concerning the effects of calcium ionophores on rodent thymocytes and the pore-forming proteins perforin and staphylococcal alpha-toxin on murine tumor cells led to the suggestion that simply raising intracellular calcium causes apoptotic cell death. This hypothesis was tested using two ionophores, A23187 and valinomycin, and ...
We previously reported the association of elevated levels of the multifunctional transcription factor, CCCTC binding factor (CTCF), in breast cancer cells with the specific anti-apoptotic function of CTCF. To understand the molecular mechanisms of this phenomenon, we investigated regulation of the human Bax gene by CTCF in breast and non-breast cells. Two CTCF binding sites (CTSs) within the Bax promoter were identified. In all cells, breast and non-breast, active histone modifications were pres ...
Progressively sophisticated understanding of cellular and molecular processes that contribute to age-related physical deterioration is being gained from ongoing research into cancer, chronic inflammatory syndromes and other serious disorders that increase with age. Particularly valuable insight has resulted from characterization of how senescent cells affect the tissues in which they form in ways that decrease an organism's overall viability. Increasingly, the underlying pathophysiology of agein ...
The mortality and morbidity rates of pancreatic cancer are high because of its extremely invasive and metastatic nature. Its lack of symptoms, late diagnosis and chemo-resistance and the ineffective treatment modalities warrant the development of new chemo-therapeutic agents for pancreatic cancer. Agents from medicinal plants have demonstrated therapeutic benefits in various human cancers. Nimbolide, an active molecule isolated from Azadirachta indica, has been reported to exhibit several medici ...
Seed germination is a result of the competition of embryonic growth potential and mechanical constraint by surrounding tissues such as the endosperm. To understand the processes occurring in the endosperm during germination, we analyzed tiling array expression data on dissected endosperm and embryo from 6 and 24 h-imbibed Arabidopsis seeds. The genes preferentially expressed in the endosperm of both 6 and 24 h-imbibed seeds were enriched for those related to cell wall biosynthesis/modifications, ...
One of the major goals of cancer therapy is the selective targeting of cancer cells over normal cells. Unfortunately, even with recent advances, the majority of chemotherapeutics still indiscriminately kill all rapidly dividing cells. Although these drugs are effective in certain settings, their inability to specifically target cancer results in significant dose-limiting toxicities. One way to avoid such toxicities is to target an aspect of the cancer cell that is not shared by normal cells. A p ...
Severe pneumonia is found in simultaneous influenza pneumonia and bacterial infection, and suggests a relationship with immunological mechanisms. Here, we performed two-dimensional gel electrophoresis to detect immunological molecules related to the fulminant pneumonia caused by influenza virus and Streptococcus pneumoniae co-infection in mice. We found two spots that were expressed strongly in co-infected mouse lungs, compared with S. pneumoniae or influenza virus singly infected mouse lungs. T ...
Previously, deficiency in the expression of the nuclear orphan receptor TAK1 was found to be associated with delayed cerebellar granule cell migration and Purkinje cell maturation with a permanent deficit in foliation of lobules VI–VII, suggesting a role for TAK1 in cerebellum development. In this study, we confirm that TAK1-deficient (TAK1−/−) mice have a smaller cerebellum and exhibit a disruption of lobules VI–VII. We extended these studies and show that at postnatal day   7, TA ...
The death domain and death effector domain are two common motifs that mediate protein-protein interactions between components of cell death signaling complexes. The mechanism by which these domains engage their binding partners has been explored by extensive mutagenesis of two death adaptors, FADD and TRADD, suggesting that a death adaptor can discriminate its intended binding partners from other proteins harboring similar motifs. Death adaptors are found to utilize one of two topologically cons ...
BACKGROUND & AIMS We previously identified that high Aurora B expression was associated with hepatocellular carcinoma (HCC) recurrence due to tumor dissemination. In this preclinical study, a novel inhibitor of Aurora B kinase was evaluated as a treatment for human HCC. METHODS AZD1152 is a selective inhibitor of Aurora B kinase. Twelve human HCC cell lines were analyzed for Aurora B kinase expression and the in vitro effects of AZD1152. The in vivo effects of AZD1152 were analyzed in a subcut ...
Sensitization of cancer cells to apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) by luteolin has been suggested by in vitro studies. However, no in vivo experiment has been reported to validate the potentiation effect of luteolin on TRAIL's anticancer activity. In this report, we first confirmed that luteolin potentiates TRAIL-induced cytotoxicity in A549 cells and HeLa cells in association with increased activation of apoptosis. Then we performed an in vivo ...
Berberine has a wide range of biochemical and pharmacologic effects, including antitumor activity, but the mechanisms involved in berberine-induced apoptosis remain unclear. The purpose of the present study was to investigate the changes in oxidative stress and endoplasmic reticulum (ER)-related molecules, which are closely associated with cell death-signaling transduction pathways, in human glioblastoma T98G cells treated with berberine. Berberine significantly decreased the cell viability of T ...
Oocyte-secreted factors (OSFs) maintain the low incidence of cumulus cell apoptosis. In this report, we described that the presence of oocytes suppressed the expression of proapoptotic protein BCL-2-interacting mediator of cell death-extra long (BIMEL) in porcine cumulus cells. Atretic (terminal deoxynucleotidyl transferase dUTP nick end labeling-positive) cumulus cells strongly expressed BIMEL protein. The healthy cumulus- oocyte complex exhibited a low BIMEL expression in cumulus cell while th ...
Arcanobacterium haemolyticum is an emerging bacterial pathogen, causing pharyngitis and more invasive infections. This organism expresses an unusual phospholipase D (PLD), which we propose promotes bacterial pathogenesis through its action on host cell membranes. The pld gene is found on a genomic region of reduced %G + C, suggesting recent horizontal acquisition. Recombinant PLD rearranged HeLa cell lipid rafts in a dose-dependent manner and this was inhibited by cholesterol sequestration. PLD ...
Tumour necrosis factor (TNF) related apoptosis-inducing ligand (TRAIL/APO2L) is a recently identified member of the TNF family, which induces programmed cell death in a variety of neoplastic cell types, but not in most nonneoplastic cells. In this study, we report on the identification of two novel alternative splice variants of TRAIL in neoplastic and non-neoplastic human cells lacking either exon 3 (TRAIL-β) or exons 2 and 3 (TRAIL-γ). In both splice variants, loss of exon 3 resulted in a fr ...
Neuronal death induced by serum deprivation (SD) in HT22-cells was accompanied by a moderate activation of caspase-3, a prominent upregulation of AIF and its translocation into the nucleus. In addition protein levels of autophagy markers such as LC3 and beclin-1 were affected by SD. The ratio of LC3-II/LC3-I was significantly increased in serum deprived cultures. Furthermore, the addition of the pan-caspase inhibitor z-VAD(OMe)-FMK (zVAD) does not protect HT22-cells from SD-induced neurodegenera ...
Transient receptor potential melastatin 2 (TRPM2), a Ca(2+)-permeable cation channel implicated in postischemic neuronal cell death, leukocyte activation, and insulin secretion, is activated by intracellular ADP ribose (ADPR). In addition, the pyridine dinucleotides nicotinamide-adenine-dinucleotide (NAD), nicotinic acid-adenine-dinucleotide (NAAD), and NAAD-2'-phosphate (NAADP) have been shown to activate TRPM2, or to enhance its activation by ADPR, when dialyzed into cells. The precise subset ...
Hyperthermia is used in cancer therapy, however much remains to be discovered regarding its mechanisms of action at the cellular level. In this study, the effects of hyperthermia on cell death, survival, morphology and the cytoskeleton were investigated in a non-small cell lung cancer cell line, H1299. Despite the fact that this cell line is widely used in research, it has not yet been tested for heat shock sensitivity. Cells were given a 30-min heat shock at 43.5°C and 45°C and left to recove ...
We observed whether the effect of tumor-associated macrophages on gastric cancer stem cell in omental milky spots and lymph nodes micrometastasis and research its possible mechanism. Macrophage THP-1 cells and Human gastric adenocarcinoma SGC-7901 cells were collectively cultivated in vivo. We found macrophage could suppress the proliferation and accelerated cell death of MFC cell. Meanwhile, these effects may be concerned with many signaling pathways, and we detected MCP-1 and COX-2 miRNA expre ...
Exposure of lung cancer cells to gemcitabine (2',2'-difluorodeoxycytidine) arrests cells in S phase and induces secondary apoptotic cell death. Gemcitabine treatment decreased the expression of IkappaB-alpha protein and, concomitantly, increased the activity of nuclear factor-kappaB (NF-kappaB) transcription factor, a known inhibitor of the apoptotic response. This increase was accompanied by a similar increment in the expression of inhibitor of apoptosis-1 (IAP-1) protein and mRNA, a caspase in ...
In the present study, the effect of a novel derivative of riccardin D (RD-N) against cancer cell lines was investigated in vitro and in vivo. We found that RD-N accumulated in the lysosomes associated with lysosomal swelling. As a result, the destabilized lysosomes induced cathepsins to release from the lysosomes into the cytosol and induced cell death which displayed features characteristic to both apoptosis and necrosis. In vivo tumor xenograft model indicated treatment of RD-N significantly r ...
www.nature.com/reviews/neuro In monkeys, the anterior bank of the intraparietal sulcus (AIP) is involved in visually guided hand movements that are relevant to grasping objects. By contrast, its caudal bank (CIP) responds to three-dimensional surface orientation. On the basis of these findings, it has been proposed that CIP conveys spatial information to AIP, affecting motor output. Now, Shikata et al. report that the equivalent areas in the human brain show a similar division of labour, and sug ...
It has been suggested that apoptosis is controlled by two intracellular sphingolipids, ceramide and sphingosine-1-phosphate (S1P), which are widely distributed in mammalian tissues. In the ovary, S1P was found to effectively block apoptosis caused by cancer therapies. Its role in male germ cell death, however, was unknown. In this study, we investigated the effects of ceramide and S1P on human male germ cell apoptosis. Germ cell death was induced by incubation of segments of seminiferous tubules ...
Intermittent fasting (IF) is neuroprotective across a range of insults, but the question of whether extending the interval between meals alters neurogenesis after ischemia remains unexplored. We therefore measured cell proliferation, cell death, and neurogenesis after transient middle cerebral artery occlusion (MCAO) or sham surgery (SHAM) in mice fed ad libitum (AL) or maintained on IF for 3 months. IF was associated with twofold reductions in circulating levels of the adipocyte cytokine leptin ...