TY - JOUR. T1 - Connexin 43 channels protect osteocytes against oxidative stress-induced cell death. AU - Kar, Rekha. AU - Riquelme, Manuel A.. AU - Werner, Sherry. AU - Jiang, Jean X.. PY - 2013/7. Y1 - 2013/7. N2 - The increased osteocyte death by oxidative stress (OS) during aging is a major cause contributing to the impairment of bone quality and bone loss. However, the underlying molecular mechanism is largely unknown. Here, we show that H2O2 induced cell death of primary osteocytes and osteocytic MLO-Y4 cells, and also caused dose-dependent decreased expression of gap junction and hemichannel-forming connexin 43 (Cx43). The decrease of Cx43 expression was also demonstrated with the treatment of other oxidants, rotenone and menadione. Antioxidant reversed the effects of oxidants on Cx43 expression and osteocyte cell death. Cx43 protein was also much lower in the osteocytes from 20-month-old as opposed to the 5-week-old or 20-week old mice. Dye transfer assay showed that H2O2 reduced the gap ...

(−)-Epigallocatechin-3-gallate (EGCG) is the most extensive studied tea polyphenol for its anti-cancer function. In this study, we report a novel mechanism of action for EGCG-mediated cell death by identifying the critical role of lysosomal membrane permeabilization (LMP). First, EGCG-induced cell death in human cancer cells (both HepG2 and HeLa) was found to be caspase-independent and accompanied by evident cytosolic vacuolization, only observable when cells were treated in serum-free medium. The cytosolic vacuolization observed in EGCG-treated cells was most probably caused by lysosomal dilation. Interestingly, EGCG was able to disrupt autophagic flux at the degradation stage by impairment of lysosomal function, and EGCG-induced cell death was independent of Atg5 or autophagy. The key finding of this study is that EGCG is able to trigger LMP, as evidenced by Lyso-Tracker Red staining, cathepsin D cytosolic translocation and cytosolic acidification. Consistently, a lysosomotropic agent, chloroquine,

TY - JOUR. T1 - How Do Cardiomyocytes Die? Apoptosis and Autophagic Cell Death in Cardiac Myocytes. AU - Kunapuli, Sanjay. AU - Rosanio, Salvatore. AU - Schwarz, Ernst R.. PY - 2006/6/1. Y1 - 2006/6/1. N2 - Background: Cell death constitutes one of the key events in biology. Historically, apoptosis and necrosis have been considered to represent the 2 fundamental forms of cell death. Apoptosis is a tightly regulated, energy-dependent process in which cell death follows a programmed set of events. Necrosis refers to the sum of degenerative changes that follow any type of cell death. Methods and Results: The role of apoptosis in development of ischemic heart disease, hypertensive heart disease, and end-stage heart failure has been well documented. Recent evidence suggests the potential role of a third mechanism of cell death, autophagy, in loss of cardiac myocytes. Autophagic cell death has been recently documented in myocardial cells from hypertrophied, failing, and hibernating myocardium. ...

P2X7 is an ATP-gated ion channel that is highly expressed by leukocytes, such as macrophages. Here, it has been demonstrated to be involved in the regulation of various cell death pathways; including apoptosis, pyroptosis, necrosis, and autophagy. However, cell death induction via P2X7 is complex and is reliant upon the nature of the stimulus, the duration of the stimulus, and the cell type investigated. Previous reports state that high extracellular ATP concentrations promote osmotic lysis, but whether positive allosteric modulation of P2X7 in the presence of lower concentrations of ATP condemns cells to the same fate is unknown. In this study, we compared cell death induced by high ATP concentrations, to cell death induced by compound K, a recently identified and potent positive allosteric modulator of P2X7. Based on our observations, we propose that high ATP concentrations induce early cell swelling, loss of mitochondrial membrane potential, plasma membrane rupture, and LDH release. ...

Programmed cell death (or apoptosis) is usually an evolutionarily conserved, genetically controlled suicide mechanism for cells that, when deregulated, can lead to developmental defects, cancers, and degenerative diseases [1, 2]. for germ cell death. We confirmed this initial observation by performing a dose-response analysis of the deletion mutant. In contrast to wild-type animals, deletion mutants did not exhibit an increase in germ cell apoptosis after exposure to increasing doses of IR (Physique?1C; see also Figure?S1 available online). This was reminiscent of loss-of-function (lf) mutants that are also resistant to IR-induced apoptosis. Therefore, we examined whether regulates germ cell death specifically, like and mutants. We found that developmental cell death was unaffected in mutants, suggesting that the rules of cell death by is usually specific to germ cells, like (Physique?1D). Finally, to determine whether the allele is usually a null, we performed a deficiency analysis by crossing ...

Programmed cell death (PCD) is a deliberate cellular suicide process. Dysfunction of PCD is implicated in various human diseases, including developmental and neurodegenerative disorders, cancer and autoimmune diseases [1]. PCD can be categorized by morphological criteria [2]. Type I cell death, known as apoptosis, is characterized by cell shrinkage, nuclear condensation, membrane blebbing, mitochondria dysfunction, loss of selectivity in membrane permeabilization, and nuclear DNA fragmentation. Lastly, cells are rapidly eliminated by phagocytosis [3]. Type II PCD refers to autophagic cell death (ACD). Autophagy is a catabolic process that disposes of various cytoplasmic components, including protein aggregates and organelles [4]. The components are sequestered by autophagosomes, which fuse with lysosomes for degradation. This process usually occurs in response to cellular stress to protect the cells. However, prolonged autophagy can cause ACD [5]. Type III cell death, called necrosis, is best ...

Dying cells often display a large-scale accumulation of autophagosomes and hence adopt a morphology called autophagic cell death. In many cases, it is agreed that this autophagic cell death is cell death with autophagy rather than cell death by autophagy. Here, we evaluate the accumulating body of l …

Hot pepper is one of the economically important crops in Asia. A large number of gene sequences, including expressed sequence tag (EST) and genomic sequences are publicly available. However, it is still a daunting task to determine gene function due to difficulties in genetic modification of a pepper plants. Here, we show the application of the virus-induced gene silencing (VIGS) repression for the study of 459 pepper ESTs selected as non-host pathogen-induced cell death responsive genes from pepper microarray experiments in Nicotiana benthamiana. Developmental abnormalities in N. benthamiana plants are observed in the 32 (7%) pepper ESTs-silenced plants. Aberrant morphological phenotypes largely comprised of three groups: stunted, abnormal leaf, and dead. In addition, by employing the combination of VIGS and Agrobacterium-mediated transient assays, we identified novel pepper ESTs that involved in Bax or INF1-mediated cell death responses. Silencing of seven pepper ESTs homologs suppressed Bax or INF1

The p38 mitogen-activated protein kinase (p38 MAPK) family, which is comprised of four protein isoforms, p38α, p38β, p38γ and p38δ, forms one of the key MAPK pathways. The p38 MAPKs are implicated in many cellular processes including inflammation, differentiation, cell growth, cell cycle and cell death. The function of p38 MAPKs in mitotic entry has been well established, but their role in mitotic progression has remained controversial. We identify p38γ MAPK as a modulator of mitotic progression and mitotic cell death. In HeLa cells, loss of p38γ results in multipolar spindle formation and chromosome misalignment, which induce a transient M phase arrest. The majority of p38γ-depleted cells die at mitotic arrest or soon after abnormal exit from M-phase. We show that p38 MAPKs are activated at the kinetochores and spindle poles throughout mitosis by kinase(s) that are stably bound to these structures. Finally, p38γ is required for the normal kinetochore localization of polo-like kinase 1 ...

Molecular deletion of transglutaminase 2 (TG2) has been shown to improve function and survival in a host of neurological conditions including stroke, Huntingtons disease, and Parkinsons disease. However, unifying schemes by which these cross-linking or polyaminating enzymes participate broadly in neuronal death have yet to be presented. Unexpectedly, we found that in addition to TG2, TG1 gene expression level is significantly induced following stroke in vivo or due to oxidative stress in vitro. Forced expression of TG1 or TG2 proteins is sufficient to induce neuronal death in Rattus norvegicus cortical neurons in vitro. Accordingly, molecular deletion of TG2 alone is insufficient to protect Mus musculus neurons from oxidative death. By contrast, structurally diverse inhibitors used at concentrations that inhibit TG1 and TG2 simultaneously are neuroprotective. These small molecules inhibit increases in neuronal transamidating activity induced by oxidative stress; they also protect neurons ...

Autophagy is a process in which cells digest their own organelles and proteins in response to nutritional starvation. Yu et al. describe a form of cell death that bears similarities to autophagy. Unlike apoptosis, which depends on activation of proteases in the caspase family, autophagic cell death in a mouse cell line was actually inhibited by caspase-8. Inhibition of expression of two genes known to function in autophagy, ATG7 and beclin 1, reduced cell death caused by inhibition of caspase-8. These findings could impact strategies for combating unwanted apoptosis that use caspase inhibitors to prevent cell death.. L. Yu, A. Alva, H. Su, P. Dutt, E. Freundt, S. Welsh, E. H. Baehrecke, M. J. Lenardo, Regulation of an ATG7-beclin 1 program of autophagic cell death by caspase-8. Science 304, 1500-1502 (2004). [Abstract] [Full Text]. ...

TY - JOUR. T1 - Therapeutic implications of disorders of cell death signalling. T2 - membranes, micro-environment, and eicosanoid and docosanoid metabolism. AU - Davidson, Jillian. AU - Rotondo, D. AU - Rizzo, Maria. AU - Leaver, Anne. PY - 2012/6/6. Y1 - 2012/6/6. N2 - Disruptions of cell death signalling occur in pathological processes, such as cancer and degenerative disease. Increased knowledge of cell death signalling has opened new areas of therapeutic research, and identifying key mediators of cell death has become increasingly important. Early triggering events in cell death may provide potential therapeutic targets, whereas agents affecting later signals may be more palliative in nature. A group of primary mediators are derivatives of the highly unsaturated fatty acids (HUFAs), particularly oxygenated metabolites such as prostaglandins. HUFAs, esterified in cell membranes, act as critical signalling molecules in many pathological processes. Currently, agents affecting HUFA metabolism ...

TY - JOUR. T1 - The wound response in fresh-cut lettuce involves programmed cell death events. AU - Iakimova, Elena T.. AU - Woltering, Ernst J.. PY - 2018/7. Y1 - 2018/7. N2 - In this work, the involvement of programmed cell death (PCD) in the wound-induced postharvest browning disorder and senescence in butterhead lettuce (Lactuca sativa L.) fresh-cuts was studied. At the wounded (cut, bruised) sites, rapid browning, loss of chlorophyll and massive cell death, accompanied with accumulation of reactive oxygen species and increased electrolyte leakage occurred in a narrow strip of tissue adjacent the injury. The dead cell morphology (protoplast and nuclei shrinkage) together with the biochemical and physiological changes resembled necrotic PCD type. With a slight delay post-wounding, senescence associated with similar cell death features was initiated in distant non-wounded sites. In addition to necrotic PCD, both in wounded and senescing tissue, the appearance of empty cell corpses was ...

At the beginning of neurogenesis, massive brain cell death occurs and more than 50% of cells are eliminated by apoptosis along with neuronal differentiation. However, few studies were conducted so far regarding the regulation of neural progenitor cells (NPCs) death during development. Because of the physiological role of cell death during development, aberration of normal apoptotic cell death is detrimental to normal organogenesis. Apoptosis occurs in not only neuron but also in NPCs and neuroblast. When growth and survival signals such as EGF or LIF are removed, apoptosis is activated as well as the induction of differentiation. To investigate the regulation of cell death during developmental stage, it is essential to investigate the regulation of apoptosis of NPCs. Neural progenitor cells were cultured from E14 embryonic brains of Sprague-Dawley rats. For in vivo VPA animal model, pregnant rats were treated with VPA (400 mg/kg S.C.) diluted with normal saline at E12. To analyze the cell death, we

Oxygen glucose deprivation (OGD)/re-oxygenation (OGDR) induces profound oxidative injury and neuronal cell death. It mimics ischemia-reperfusion neuronal injury. CPI-1189 is a novel tumor necrosis factor alpha-inhibiting compound with potential neuroprotective function. Here in SH-SY5Y neuronal cells and primary murine cortical neurons, CPI-1189 pretreatment potently inhibited OGDR-induced viability reduction and cell death. In OGDR-stimulated neuronal cells, p38 phosphorylation was blocked by CPI-1189. In addition, CPI-1189 alleviated OGDR-induced reactive oxygen species production, lipid peroxidation, and glutathione consumption. OGDR-induced neuronal cell apoptosis was also inhibited by CPI-1189 pretreatment. Furthermore, in SH-SY5Y cells and cortical neurons, CPI-1189 alleviated OGDR-induced programmed necrosis by inhibiting mitochondrial p53-cyclophilin D-adenine nucleotide translocase 1 association, mitochondrial depolarization, and lactate dehydrogenase release to the medium. In summary, CPI-1189

Cell death is the event of a biological cell ceasing to carry out its functions. This may be the result of the natural process of old cells dying and being replaced by new ones, or may result from such factors as disease, localized injury, or the death of the organism of which the cells are part. Kinds of cell death include the following: Programmed cell death (or PCD) is cell death mediated by an intracellular program. PCD is carried out in a regulated process, which usually confers advantage during an organisms life-cycle. For example, the differentiation of fingers and toes in a developing human embryo occurs because cells between the fingers apoptose; the result is that the digits are separate. PCD serves fundamental functions during both plant and metazoa (multicellular animals) tissue development. Apoptosis or Type I cell-death, and autophagy or Type II cell-death are both forms of programmed cell death, while necrosis is a non-physiological process that occurs as a result of infection or ...

Cancer cells increase glucose metabolism to support aerobic glycolysis. However, only some cancer cells are acutely sensitive to glucose withdrawal, and the underlying mechanism of this selective sensitivity is unclear. We showed that glucose deprivation initiates a cell death pathway in cancer cells that is dependent on the kinase RIPK1. Glucose withdrawal triggered rapid plasma membrane depolarization and an influx of extracellular calcium into the cell through the L-type calcium channel Cav1.3 (CACNA1D), followed by activation of the kinase CAMK1. CAMK1 and the demethylase PPME1 were required for the subsequent demethylation and inactivation of the catalytic subunit of the phosphatase PP2A (PP2Ac) and the phosphorylation of RIPK1. Plasma membrane depolarization, PP2Ac demethylation, and cell death were prevented by glucose and, unexpectedly, by its nonmetabolizable analog 2-deoxy-d-glucose (2-DG), a glycolytic inhibitor. These findings reveal a previously unknown function of glucose as a ...

Most schemes for TGs role in acute and chronic neurodegeneration have centered around the ability of these enzymes to cross-link mutated and/or accumulated proteins in a host of diseases, including AD, HD, and PD (Caccamo et al., 2010). And while this model unifies diseases associated with proteotoxicity, it fails to account for the benefits of molecular or pharmacological TG deletion in ischemic (Hwang et al., 2009; Colak et al., 2011) or hemorrhagic stroke (Okauchi et al., 2009). Indeed, exciting new data on the role of TG in autophagosome formation (DEletto et al., 2009), in inhibiting axonal transport of growth factors such as BDNF (Borrell-Pagès et al., 2006), in repressing adaptive gene expression (McConoughey et al., 2010), and on influencing nuclear actin dynamics (Munsie et al., 2011) have focused attention on biological roles of these fascinating enzymes other than cross-linking. Here, we demonstrate that TG is a necessary component of oxidative stress-induced death signaling in ...

During development, large numbers of cells die by a nonpathological process referred to as programmed cell death. In many tissues, dying cells display similar changes in morphology and chromosomal DNA organization, which has been termed apoptosis. Apoptosis is such a widely documented phenomenon that many authors have assumed all programmed cell deaths occur by this process. Two well-characterized model systems for programmed cell death are (i) the death of T cells during negative selection in the mouse thymus and (ii) the loss of intersegmental muscles of the moth Manduca sexta at the end of metamorphosis. In this report we compare the patterns of cell death displayed by T cells and the intersegmental muscles and find that they differ in terms of cell-surface morphology, nuclear ultrastructure, DNA fragmentation, and polyubiquitin gene expression. Unlike the T cells, which are known to die via apoptosis, we find that the intersegmental muscles display few of the features that characterize ...

Lesion mimic mutants spontaneously produce disease spots in the absence of biotic or abiotic stresses. Analyzing lesion mimic mutants sheds light on the mechanisms underlying programmed cell death and defense-related responses in plants. Here, we isolated and characterized the rice (Oryza sativa) spotted leaf 36 (spl36) mutant, which was identified from an ethyl methanesulfonate-mutagenized japonica cultivar Yundao population. spl36 displayed spontaneous cell death and enhanced resistance to rice bacterial pathogens. Gene expression analysis suggested that spl36 functions in the disease response by upregulating the expression of defense-related genes. Physiological and biochemical experiments indicated that more cell death occurred in spl36 than the wild type and that plant growth and development were affected in this mutant. We isolated SPL36 by map-based cloning. A single base substitution was detected in spl36, which results in a cysteine-to-arginine substitution in SPL36. SPL36 is predicted to

BNIP3 is a cell death-inducing mitochondrial protein that is part of a Bcl-2 subfamily with NIX and ceBNIP3. BNIP3-induced cell death morphologically resembles necrosis that is characterized by rapid plasma membrane damage and mitochondrial dysfunction in the early stages, followed by DNA fragmentation and chromatin condensation characteristic of apoptotic cell death in the later stages. DNA fragmentation during most types of apoptosis is predominantly due to caspase-3 activation. However, BNIP3-induced cell death is independent of caspase-3 activity, thus the mechanism of BNIP3-induced DNA fragmentation remains unknown. Co-immunoprecipitation analysis revealed an interaction between BNIP3, NIX, and caspase-2. The interaction is unique in that it is not mediated through the caspase-2 prodomain. Caspases-1, -8, and -9, which have homologous prodomains to caspase-2, do not bind BNIP3 or NIX, indicating specificity for caspase-2. Further structural analysis indicated that the transmembrane domain ...

TY - JOUR. T1 - The role of vacuole in plant cell death. AU - Hara-Nishimura, I.. AU - Hatsugai, N.. N1 - Funding Information: Acknowledgements. We are grateful to the Ministry of Education, Culture, Sports, Science, and Technology of Japan (MEXT) for Grants-in-Aid for Scientific Research (no. 22000014) and for the Global Center of Excellence Program Formation of a Strategic Base for Biodiversity and Evolutionary Research: from Genome to Ecosystem.. PY - 2011/8. Y1 - 2011/8. N2 - Almost all plant cells have large vacuoles that contain both hydrolytic enzymes and a variety of defense proteins. Plants use vacuoles and vacuolar contents for programmed cell death (PCD) in two different ways: for a destructive way and for a non-destructive way. Destruction is caused by vacuolar membrane collapse, followed by the release of vacuolar hydrolytic enzymes into the cytosol, resulting in rapid and direct cell death. The destructive way is effective in the digestion of viruses proliferating in the cytosol, ...

Cell death can occur through 3 mechanisms: apoptosis, autophagy, and necrosis. Apoptosis, or programmed cell death, results in controlled cell shrinkage and nuclear fragmentation via the action of caspases, as well as an anti-inflammatory cytokine release. In contrast, necrosis signals via RIPK1 (RIP1), leading to cell swelling, lysis, and a pro-inflammatory cytokine release. Autophagy destroys the cells damaged proteins and organelles via an intracellular catabolic process in the lysosome. Multiple physiological processes require the removal of specific cells by a controlled cell-death program. For example, tissue remodeling activates apoptosis, whereas energy metabolism and growth regulation responses rely on autophagy. Developmental processes often activate apoptosis, while bodily injuries or infection more commonly induce necrosis. The molecular mechanisms behind these cell death pathways overlap, and can be co-activated during some cellular functions. Apoptosis and necrosis both signal ...

FIG. 2. Dose- and time-dependent effects of SERCA inhibition on CHOP expression, caspase-3 activation, and cell death. Cell death was assayed in real-time by propidium iodide incorporation in MIN6 cells. A: Images illustrating the progressive propidium iodide incorporation in a field of MIN6 cells exposed to 1 μmol/l thapsigargin (Tg). B: Representative time course of cell death in response to various concentrations of thapsigargin. ○, Control; ▪, 0.01 μmol/l thapsigargin; ▴, 0.1 μmol/l thapsigargin; •, 1 μmol/l thapsigargin. C: Dose dependence of the thapsigargin-induced MIN6 cell death, quantified as the area under the curves (IAUC) of the first 24 h of the propidium iodide incorporation profiles (n = 3). D: Induction of CHOP (∼31-kDa band) and cleaved caspase-3 (∼17- to 19-kDa band) in MIN6 cells cultured for 24 h in DMEM containing 25 mmol/l glucose and increasing concentrations of thapsigargin (n = 3). E: Representative real-time imaging of caspase-3 activation in living ...

The present study aimed to investigate anti-proliferative and apoptotic effects of quercetin on human leukemia cells and effects of quercetin-induced cell death on a nov..

Programmed cell death (or PCD) is the death of a cell in any form, mediated by an intracellular program. PCD is carried out in a biological process, which usually confers advantage during an organisms life-cycle. For example, the differentiation of fingers and toes in a developing human embryo occurs because cells between the fingers apoptose; the result is that the digits are separate. PCD serves fundamental functions during both plant and animal tissue development. Apoptosis and autophagy are both forms of programmed cell death, but necrosis was long seen as a non-physiological process that occurs as a result of infection or injury. Necrosis is the death of a cell caused by external factors such as trauma or infection and occurs in several different forms. Recently a form of programmed necrosis, called necroptosis, has been recognized as an alternate form of programmed cell death. It is hypothesized that necroptosis can serve as a cell-death backup to apoptosis when the apoptosis signaling is ...

Excitotoxic cell death, the end for many cells after ischemic brain injury and in some neurodegenerative diseases, is triggered by glutamate-induced calcium influx. Downstream, activation of the p38α map kinase leads to apoptosis, but just how calcium and p38 connect has been an open question. New results from Michael Courtneys lab at the University of Kuopio in Finland show that the small GTPase Rho is the missing link. Their work, published in the March 18 online edition of Nature Neuroscience, establishes Rho activation by calcium influx as a necessary and sufficient event to turn on p38 and cause cell death in primary neurons.. Their results open up a potential new target for drugs to block excitotoxicity, and may have some additional relevance to Alzheimer disease. Inhibitors of Rho and its downstream kinase Rock can modulate amyloid-β (Aβ) peptide production (Zhou et al., 2003; Leuchtenberger et al., 2006). In addition, Rho is farnesylated, and changes in Rho/Rock pathway activity have ...

Cell death is not only an essential phenomenon in normal development and homeostasis, but also crucial in various pathologies. It is now clear that many types of cell death can be regulated by pharmacological or genetic interventions. These were largely achieved by identifying the molecular mechanisms underlying the regulated cell death (RCD). While in the immune system, RCD needs to be facilitated to help the clearance of pathogens and tumors, in healthy cells, especially the terminally differentiated neurons in the nervous system, it is more desirable to protect cells from dying due to stress under pathological conditions. Thus, understating the inhibitory and the activating signals for RCD in different systems is important. In this thesis, I will discuss the study of two key molecules involved in RCD: programmed death 1 (PD-1, as inhibitor for RCD) and serine/threonine kinase receptor interaction protein 3 (RIP3, as promoter for RCD) in two different systems. First, I studied the role of PD-1

Dive into the research topics of Neuronal death in amyotrophic lateral sclerosis is apoptosis: Possible contribution of a programmed cell death mechanism. Together they form a unique fingerprint. ...

Although it is well established that IFNγ causes cell death in a variety of cell types (Deiss et al., 1995; Ossina et al., 1997; Wen et al., 1997; Ruiz-Ruiz et al., 2000; Trautmann et al., 2000; Horiuchi et al., 2006), the signal transduction downstream of STAT1 remains largely unknown (Barber, 2000). Unraveling the role of IFNγ in apoptosis remains a challenge because IFNγ may prime cells to apoptosis and through induction of many genes can concomitantly elicit an antiproliferative and a proliferative state (Xiang et al., 2008). The decision between life and death may depend on possible costimuli or the cell type. Enhanced expression and translocation of Diablo into the cytosol play a critical role in the promotion of IFNγ-induced apoptosis of IFNγ-sensitive B cells (Yoshikawa et al., 2001). Th1 cells that secrete high levels of IFNγ are more susceptible to activation-induced cell death than Th2 cells because Th2 cells express Fas-associated phosphatase, FAP-1 (Zhang et al., 1997). In ...

03.05.2016 The Gutenberg Research College (GRC) of Johannes Gutenberg University Mainz (JGU) has chosen to give the 2016 Gutenberg Research Award to American biomedical researcher Dr. Vishva Dixit for his groundbreaking work in the field of programmed cell death. His findings have contributed significantly to the understanding of the actual mechanisms involved in the crucial process that is also known as apoptosis. At the same time, Dixit is also helping to convert the information obtained into a form that can be employed in clinical applications. In the person of Dr. Vishva Dixit, the Gutenberg Research College is bestowing the Gutenberg Research Award on an internationally acclaimed top-level researcher. His groundbreaking findings on cell death have provided important clues that help us understand in much more detail the processes associated with the immune system, emphasized the Director of the Gutenberg Research College, Professor Matthias Neubert. Programmed cell death is actually a ...

TY - JOUR. T1 - Comparative analysis of the role of small G proteins in cell migration and cell death. T2 - Cytoprotective and promigratory effects of RalA. AU - Jeon, Hyejin. AU - Zheng, Long Tai. AU - Lee, Shinrye. AU - Lee, Won Ha. AU - Park, Nammi. AU - Park, Jae-Yong. AU - Heo, Won Do. AU - Lee, Myung Shik. AU - Suk, Kyoungho. PY - 2011/1/1. Y1 - 2011/1/1. N2 - Small G protein superfamily consists of more than 150 members, and is classified into six families: the Ras, Rho, Rab, Arf, Ran, and RGK families. They regulate a wide variety of cell functions such as cell proliferation/differentiation, cytoskeletal reorganization, vesicle trafficking, nucleocytoplasmic transport and microtubule organization. The small G proteins have also been shown to regulate cell death/survival and cell shape. In this study, we compared the role of representative members of the six families of small G proteins in cell migration and cell death/survival, two cellular phenotypes that are associated with ...

Balakireva A. V., Zamyatnin Jr A. A. Cutting out the gaps between proteases and programmed cell death // Frontiers in plant science. - 2019. - Vol. 10. - P. 704. To date, many animal models for programmed cell death (PCD) have been extensively characterized and classified while such efforts in plant types of PCD still remain poorly understood. However, despite a wide range of functional differences between PCD types in animals and plants, it is certain that all of them are regulated through the recruitment of proteases. Most importantly, proteases are able to perform proteolysis that results in a gain or loss of protein function. This principle relies on the presence of proteolytic cascades where proteases are activated upon various upstream stimuli and which lead to repetitive cell death. While protease activation, proteolytic cascades and targeted substrates are described in detail mainly for nematode, human, and mice models of apoptosis, for plants, only fragmentary knowledge of protease ...

Finland Deaths Stats, NationMaster. Retrieved from http://www.nationmaster.com/country-info/profiles/Finland/Health/Deaths. Finland Deaths Stats, NationMaster. 1948-2012. ,http://www.nationmaster.com/country-info/profiles/Finland/Health/Deaths,.. Finland Deaths Stats, NationMaster, ,http://www.nationmaster.com/country-info/profiles/Finland/Health/Deaths, [assessed 1948-2012]. Finland Deaths Stats, NationMaster [Internet]. 1948-2012. Avaliable from: ,http://www.nationmaster.com/country-info/profiles/Finland/Health/Deaths,.. Finland Deaths Stats, NationMaster. Avaliable at: nationmaster.com. Assessed 1948-2012.. Finland Deaths Stats, NationMaster, http://www.nationmaster.com/country-info/profiles/Finland/Health/Deaths (assessed 1948-2012). Finland Deaths Stats, NationMaster, http://www.nationmaster.com/country-info/profiles/Finland/Health/Deaths (last visited 1948-2012). Finland Deaths Stats, NationMaster, http://www.nationmaster.com/country-info/profiles/Finland/Health/Deaths (as ...

Disruption of the reprogrammed energy management system of malignant cells is a prioritized goal of targeted cancer therapy. Two regulators of this system are the Fer kinase, and its cancer cell specific variant, FerT, both residing in subcellular compartments including the mitochondrial electron transport chain. Here, we show that a newly developed inhibitor of Fer and FerT, E260, selectively evokes metabolic stress in cancer cells by imposing mitochondrial dysfunction and deformation, and onset of energy-consuming autophagy which decreases the cellular ATP level. Notably, Fer was also found to associate with PARP-1 and E260 disrupted this association thereby leading to PARP-1 activation. The cooperative intervention with these metabolic pathways leads to energy crisis and necrotic death in malignant, but not in normal human cells, and to the suppression of tumors growth in vivo. Thus, E260 is a new anti-cancer agent which imposes metabolic stress and cellular death in cancer cells. The tyrosine

Scale?bars denote 50 m. Open in a separate window Figure 7 Correlation among cell death, nitric oxide (NO) and autophagy in tobacco BY-2 cells after 24 h of toxin (AaT) exposure. After 24 h, AaT facilitated Ca2+ influx with an accumulation of reactive oxidant intermediates and NO, to manifest necrotic cell death. Inhibition of NO accumulation by 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) decreased the level of necrotic cell death, and induced autophagy, which suggests NO accumulation represses autophagy and facilitates necrotic cell death at 24 h. Application of N-acetyl-L-cysteine at 3 h, 666-15 confirmed ROS to be the key initiator of autophagy, and together with cPTIO for 24 h, revealed the combined effects of NO and ROS is required for necrotic HR cell death. and plants with silenced or knocked-out (Fr.) Keissler causes a serious worldwide depletion of economic yield30. In (tobacco), the pathogen has been reported to inculcate lethal symptoms like anthracnose, ...

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Glioma-initiating cells (GIC) are considered the underlying cause of recurrences of aggressive glioblastomas, replenishing the tumor population and undermining the efficacy of conventional chemotherapy. Here we report the discovery that inhibiting T-type voltage-gated Ca2+ and KCa channels can effectively induce selective cell death of GIC and increase host survival in an orthotopic mouse model of human glioma. At present, the precise cellular pathways affected by the drugs affecting these channels are unknown. However, using cell-based assays and integrated proteomics, phosphoproteomics, and transcriptomics analyses, we identified the downstream signaling events these drugs affect. Changes in plasma membrane depolarization and elevated intracellular Na+, which compromised Na+-dependent nutrient transport, were documented. Deficits in nutrient deficit acted in turn to trigger the unfolded protein response and the amino acid response, leading ultimately to nutrient starvation and GIC cell death. ...

During development of the nervous system, as many as half of all neurons generated are ultimately eliminated by a process known as programmed cell death. Much of this cell death occurs as newly differentiated neurons compete for limiting amounts of survival-promoting neurotrophic factors. Though counterintuitive, the selective death of neurons at specific times during development is critical for sculpting a properly wired nervous system. While programmed cell death is essential for normal development, too much or too little cell death later in life is a confounding factor in diseases ranging from Alzheimers disease and stroke to brain cancer. Research in the Freeman laboratory is aimed at characterizing the mechanisms that regulate cell death in the mammalian nervous system. More specifically, we aim to identify and understand the critical cell signaling events that, if left unchecked, commit a neuron to die ...

JUPITER, FL - January 27, 2015 - In a pair of related studies, scientists from the Florida campus of The Scripps Research Institute (TSRI) have shown their drug candidates can target biological...

1. Lipid-induced cell death - Investigation of the mechanism leading to lipotoxicity. 2. Meiotic Processes within the regulation of aging - characterization of the mechanism leading to longevity in yeast and mammalian cells. 3. Autophagy (self-eating) in dying cells - Interconnection of apoptosis and autophagy via a new Bcl-2 family-protein. 4. Identification of a novel yeast caspase - Functional analysis of the raptor- protein regarding the regulation of autophagy and apoptosis. 5. Yeast as a model for neurodegeneration - Parkinson´s, Alzheimer`s, and Huntington`s disease. 6. Caspase independent regulation of cell death - implications of apoptosis-inducing factor AIF1 and its interactom in aging and apoptosis. Contact: Prof. Dr. Frank Madeo. ...

Drug resistance has been mostly explained by molecular changes, such as overexpression of p-glycoprotein or O6-methylguanine-DNA-methyltransferase, which interfere with drug actions on the targets (1 , 2) . Because most anticancer agents, regardless of their diverse targets, exert effects by inducing apoptosis via activation of apoptotic pathways common to many cellular stresses, any antiapoptotic changes disrupting the common intrinsic pathways to execute physiological cell death can also make malignant cells resistant to chemotherapy (3) . Such alterations opposing apoptosis are routinely observed in malignant tumors, including both the functional loss of tumor suppressors p53, Bax, or PTEN and deregulated hyperfunction of oncogenic proteins, such as Ras, Bcl-2, and PI3K 2 ,(3) .. In tumor cells with an aberrantly activated PI3K/Akt survival pathway, the increased antiapoptotic signals overcome apoptotic signals of anticancer drugs, confer drug resistance on the tumor cells, and result in a ...

Cells of the Monocyte / Macrophage lineage are key players in innate and adaptive immunity. They eliminate pathogens through their phagocytic and antimicrobial properties, secretion of inflammatory and immunoregulatory cytokines, as well as their capacity to present foreign antigens to T lymphocytes in lymphoid tissues. The importance of M/Ms in the immune response require them to undergo strict regulation, which occurs, at least in part, through the control of monocytic cell survival. Autophagy is a ubiquitous cellular process by which cells degrade intracellular, cytoplasmic components via a network of interconnected vacuoles to carry out a variety of functions. Autophagy typically functions in maintaining cellular homeostasis and mitigating stresses. However, more recent studies have shown that autophagy may play a role in cell death. Our laboratory has previously found that the cytokine IFNγ can induce cell death in human monocytes in an autophagy-dependent manner. Conversely, IL-10 ...

Inflammasome Lab researchers, Associate Professor Kate Schroder and Dr Dave Boucher, are looking forward to the 2nd Japan Australia Meeting on Cell Death, in Tokyo 22-23 May 2018.

Roscoff, May 17th, 2021. SeaBeLife, a pharmaceutical company focused on identifying a new class of drug candidates able to deprogram regulated cell death, announces its second seed money fundraising with several Business Angels networks.. The companys disruptive technology is based on inhibiting simultaneously two kinds of necrotic cell deaths. The therapeutic potential is major because simultaneous activation has been recently pointed as an explanation for acute pathologies, which have limited therapeutic options and are notoriously hard to treat.. In particular SeaBeLife has confirmed the promising in vivo preliminary results obtained in 2020 for two indications: acute renal failure and liver failure. Beyond acute pathologies, SeaBeLife is also looking into chronical diseases such as Parkinsons, Alzheimers, or AMD (retinal degeneration). Encouraging preliminary results were generated in vitro for all these three chronic indications. The team is presently performing in vivo ...

Extensive programmed cell death (PCD) occurs in the developing nervous system. Neuronal death occurs, at least in part, because neurons are produced in excess during development and compete with each other for the limited amounts of the survival-promoting trophic factors secreted by target tissues. Neuronal death is apoptotic and utilizes components that are conserved in other PCD pathways. In this review, we discuss the mechanism of trophic factor-dependent neuronal cell death by focusing on the pathway of nerve growth factor (NGF) deprivation-induced sympathetic neuronal death. We describe the biochemical and genetic events that occur in NGF-deprived sympathetic neurons undergoing PCD. Participation of the Bcl-2 family of proteins and the interleukin-1β-converting enzyme family of proteases (caspases) in this and other models of neuronal death is also examined. The order and importance of these components during NGF deprivation-induced sympathetic neuronal death are discussed.. ...

The role of these enzymes in programmed cell death was first identified in 1993, with their functions in apoptosis well characterised. This is a form of programmed cell death, occurring widely during development, and throughout life to maintain cell homeostasis. Activation of caspases ensures that the cellular components are degraded in a controlled manner, carrying out cell death with minimal effect on surrounding tissues.[3]. Caspases have other identified roles in programmed cell death such as pyroptosis and necroptosis. These forms of cell death are important for protecting an organism from stress signals and pathogenic attack. Caspases also have a role in inflammation, whereby it directly processes pro-inflammatory cytokines such as pro-IL1β. These are signalling molecules that allow recruitment of immune cells to an infected cell or tissue. There are other identified roles of caspases such as cell proliferation, tumour suppression, cell differentiation, neural development and axon ...

Mitochondrial regulation of cell death: a phylogenetically conserved control - Mitochondria are fundamental for eukaryotic cells as they participate in critical catabolic and anabolic pathways. Moreover, mitochondria play a key role in the signal transduction cascades that precipitate many (but not all) regulated variants of cellular demise. In this short review, we discuss the differential implication of mitochondria in the major forms of regulate cell death.

Cellular decisions to live or die are fundamental to development and adult homeostasis, playing roles in a wide variety of physiological and pathological processes. These include cancer, degenerative disease, innate and adaptive immunity, ischemia-reperfusion injury, and infectious disease. As the study of cell death moves beyond the central mechanisms of apoptosis to wider issues of regulation and other forms of cell death, this vibrant area of research widens its influence and importance for human health and disease.

The MAP kinase p38 is activated by noncanonical BMP signaling, and also by cellular stress, with p38 activity providing a second readout of intrinsic and extrinsic function. If Gdf6a promotes apoptosis by increasing cell stress, upregulated p38 activity would be observed in mutants, while the converse would occur if p38 is a mediator of Gdf6a signaling. Compared with gdf6a+/+ siblings (Fig. 4A), gdf6a−/− embryos exhibit markedly increased ocular p38 MAP kinase phosphorylation assessed with whole-mount IHC using phospho-specific (Thr180/Tyr182) p38 MAP kinase antibodies (Fig. 4B). If such increased levels of phosphorylated-p38 MAP kinases activate apoptosis, inhibition of this kinase would be expected to rescue the gdf6a −/− cell death phenotype. To test this, we applied a pharmacologic inhibitor of p38 MAP kinase (SB203580 [60 μM]) to zebrafish embryos and examined apoptosis using caspase-3 IHC. Treatment with SB203580 partially inhibits the increased ocular caspase-3 activation of ...