Tenascin-C induces resistance to apoptosis in pancreatic cancer cell through activation of ERK/NF-κB pathway
In this study, we performed an analysis to determine the effects of TNC on modulating cell apoptosis and chemo-resistance and explored its mechanisms involving activation in pancreatic cancer cell. The expressions of TNC, ERK1/2/p-ERK1/2, Bcl-xL and Bcl-2 were detected by immunohistochemistry and western blotting. Then the effects of exogenous and endogenous TNC on the regulation of tumor proliferation, apoptosis and gemcitabine cytotoxicity were investigated. The associations among the TNC knockdown, TNC stimulation and expressions of ERK1/2/NF-κB/p65 and apoptotic regulatory proteins were also analyzed in cell line...
Source: Apoptosis - February 18, 2015 Category: Molecular Biology Source Type: research

Autophagy in the light of sphingolipid metabolism
Abstract Maintenance of cellular homeostasis requires tight and coordinated control of numerous metabolic pathways, which are governed by interconnected networks of signaling pathways and energy-sensing regulators. Autophagy, a lysosomal degradation pathway by which the cell self-digests its own components, has over the past decade been recognized as an essential part of metabolism. Autophagy not only rids the cell of excessive or damaged organelles, misfolded proteins, and invading microorganisms, it also provides nutrients to maintain crucial cellular functions. Besides serving as essential structural moieties o...
Source: Apoptosis - February 15, 2015 Category: Molecular Biology Source Type: research

Targeting of tumor-associated gangliosides with antibodies affects signaling pathways and leads to cell death including apoptosis
Abstract Gangliosides are a diverse group of sialic acid containing glycosphigolipids that are abundantly present in an outer plasma membrane of some cells. Biological roles of gangliosides and other lipids in cell fate regulation are being extensively studied. Gangliosides are well known to be involved in interactions between cells and in signal transduction to regulate growth, adhesion and motility. Moreover, many gangliosides are tumor-associated antigens over-expressed on several tumor types. As a result, monoclonal antibodies binding gangliosides can be used to diagnose, monitor and to treat cancer patients. ...
Source: Apoptosis - February 12, 2015 Category: Molecular Biology Source Type: research

Carbon ion beam triggers both caspase-dependent and caspase-independent pathway of apoptosis in HeLa and status of PARP-1 controls intensity of apoptosis
The objective of our study was to find mechanism(s) of induction of apoptosis by CIB and role of PARP-1 in CIB-induced apoptosis. We observed overall higher apoptosis in PARP-1 knocked down HeLa cells (HsiI) compared with negative control H-vector cells after irradiation with CIB (0–4 Gy). CIB activated both intrinsic and extrinsic pathways of apoptosis via caspase-9 and caspase-8 activation respectively, followed by caspase-3 activation, apoptotic body, nucleosomal ladder formation and sub-G1 accumulation. Apoptosis inducing factor translocation into nucleus in H-vector but not in HsiI cells after CIB irradiati...
Source: Apoptosis - February 11, 2015 Category: Molecular Biology Source Type: research

The effects of humanin and its analogues on male germ cell apoptosis induced by chemotherapeutic drugs
In this study we showed that HN ameliorated chemotherapy [cyclophosphamide (CP) and Doxorubicin (DOX)]-induced male germ cell apoptosis both ex vivo in seminiferous tubule cultures and in vivo in the testis. HN acts by several putative mechanisms via binding to: an IL-12 like trimeric membrane receptor; BAX; or insulin-like growth factor binding protein-3 (IGFBP-3, a proapoptotic factor). To understand the mechanisms of HN on male germ cell apoptosis, we studied five HN analogues including: HNG (HN-S14G, a potent agonist), HNG-F6A (no binding to IGFBP-3), HN-S7A (no self-dimerization), HN-C8P (no binding to BAX), and HN-L1...
Source: Apoptosis - February 9, 2015 Category: Molecular Biology Source Type: research

The emerging role of Acid Sphingomyelinase in autophagy
Abstract Autophagy, the main intracellular process of cytoplasmic material degradation, is involved in cell survival and death. Autophagy is regulated at various levels and novel modulators of its function are being continuously identified. An intriguing recent observation is that among these modulators is the sphingolipid metabolising enzyme, Acid Sphingomyelinase (A-SMase), already known to play a fundamental role in apoptotic cell death participating in several pathophysiological conditions. In this review we analyse and discuss the relationship between autophagy and A-SMase describing how A-SMase may regulate ...
Source: Apoptosis - February 9, 2015 Category: Molecular Biology Source Type: research

The unfolded protein response in the therapeutic effect of hydroxy-DHA against Alzheimer’s disease
Abstract The unfolded protein response (UPR) and autophagy are two cellular processes involved in the clearing of intracellular misfolded proteins. Both pathways are targets for molecules that may serve as treatments for several diseases, including neurodegenerative disorders like Alzheimer’s disease (AD). In the present work, we show that 2-hydroxy-DHA (HDHA), a docosahexaenoic acid (DHA) derivate that restores cognitive function in a transgenic mouse model of AD, modulates UPR and autophagy in differentiated neuron-like SH-SY5Y cells. Mild therapeutic HDHA exposure induced UPR activation, characterized by...
Source: Apoptosis - February 8, 2015 Category: Molecular Biology Source Type: research

Role of mitochondrial raft-like microdomains in the regulation of cell apoptosis
Abstract Lipid rafts are envisaged as lateral assemblies of specific lipids and proteins that dissociate and associate rapidly and form functional clusters in cell membranes. These structural platforms are not confined to the plasma membrane; indeed lipid microdomains are similarly formed at subcellular organelles, which include endoplasmic reticulum, Golgi and mitochondria, named raft-like microdomains. In addition, some components of raft-like microdomains are present within ER–mitochondria associated membranes. This review is focused on the role of mitochondrial raft-like microdomains in the regulation of...
Source: Apoptosis - February 5, 2015 Category: Molecular Biology Source Type: research

Lactosylceramide-accumulation in lipid-rafts mediate aberrant-autophagy, inflammation and apoptosis in cigarette smoke induced emphysema
Abstract Ceramide-accumulation is known to be involved in the pathogenesis of chronic inflammatory lung diseases including cigarette smoke-induced emphysema (CS-emphysema) but the exact sphingolipid metabolite that initiates emphysema progression remains ambiguous. We evaluated here a novel role for the sphingolipid, lactosylceramide (LacCer), as a potential mechanism for pathogenesis of CS-emphysema. We assessed the expression of LacCer, and LacCer-dependent inflammatory, apoptosis and autophagy responses in lungs of mice exposed to CS, as well as peripheral lung tissues from COPD subjects followed by experimenta...
Source: Apoptosis - February 1, 2015 Category: Molecular Biology Source Type: research

Glycosphingolipids and cell death: one aim, many ways
Abstract Glycosphingolipids (GSLs) are a family of bioactive lipids that in addition to their role in the regulation of structural properties of membrane bilayers have emerged as crucial players in many biological processes and signal transduction pathways. Rather than being uniformly distributed within membrane bilayers, GSLs are localized in selective domains called lipid rafts where many signaling platforms operate. One of the most important functions of GSLs, particularly ceramide, is their ability to regulate cell death pathways and hence cell fate. This complex role is accomplished by the ability of GSLs to ...
Source: Apoptosis - January 31, 2015 Category: Molecular Biology Source Type: research

Ceramide in the regulation of eryptosis, the suicidal erythrocyte death
Abstract Similar to apoptosis of nucleated cells, erythrocytes may undergo eryptosis, a suicidal death characterized by cell shrinkage and phospholipid scrambling of the cell membrane leading to phosphatidylserine exposure at the cell surface. As eryptotic erythrocytes are rapidly cleared from circulating blood, excessive eryptosis may lead to anemia. Moreover, eryptotic erythrocytes may adhere to the vascular wall and thus impede microcirculation. Stimulators of eryptosis include osmotic shock, oxidative stress and energy depletion. Mechanisms involved in the stimulation eryptosis include ceramide formation which...
Source: Apoptosis - January 31, 2015 Category: Molecular Biology Source Type: research

Membrane lipid rafts and estrogenic signalling: a functional role in the modulation of cell homeostasis
Abstract It has become widely accepted that along with their ability to directly regulate gene expression, estrogens also influence cell signalling and cell function via rapid membrane-initiated events. Many of these signalling processes are dependent on estrogen receptors (ER) localized to the plasma membrane. However, the mechanisms by which ER are able to trigger cell signalling when targeted to the membrane surface have to be determined yet. Lipid rafts seem to be essential for the plasma membrane localization of ER and play a critical role in their membrane-initiated effects. In this review, we briefly recapi...
Source: Apoptosis - January 31, 2015 Category: Molecular Biology Source Type: research

Lysophosphatidic acid rescues bone mesenchymal stem cells from hydrogen peroxide-induced apoptosis
In this study, we report that H2O2 induces rat BMSC apoptosis whereas LPA pre-treatment effectively protects BMSCs from H2O2-induced apoptosis. LPA protection of BMSC from the induced apoptosis is mediated mostly through LPA3 receptor. Furthermore, we found that membrane G protein Gi2 and Gi3 are involved in LPA-elicited anti-apoptotic effects through activation of ERK1/2- and PI3 K-pathways. Additionally, H2O2 increases levels of type II of light chain 3B (LC3B II), an autophagy marker, and H2O2-induced autophagy thus protected BMSCs from apoptosis. LPA further increases the expression of LC3B II in the presence of H2O2. ...
Source: Apoptosis - January 30, 2015 Category: Molecular Biology Source Type: research

Augmenter of liver regeneration plays a protective role against hydrogen peroxide-induced oxidative stress in renal proximal tubule cells
Abstract Oxidative stress plays an important role in cellular destruction. Augmenter of liver regeneration (ALR) is an anti-apoptotic factor that is expressed in all mammalian cells and functions as an anti-oxidant by stimulating the expression of a secretory isoform of clusterin and inhibiting reactive oxygen species (ROS) generation. Previous work from our group showed that ALR expression is upregulated in acute kidney injury (AKI) rats, and recombinant human ALR reduces tubular injury. In the present study, we used small interfering RNA (siRNA) silencing of ALR to examine its role in H2O2 induced mitochondrial ...
Source: Apoptosis - January 30, 2015 Category: Molecular Biology Source Type: research

Calcium signals inhibition sensitizes ovarian carcinoma cells to anti-Bcl-x L strategies through Mcl-1 down-regulation
Abstract Ovarian carcinoma is the leading cause of death from gynecologic cancer in the developed world and is characterized by acquired chemoresistance leading to an overall 5-year survival rate of about 30 %. We previously showed that Bcl-xL and Mcl-1 cooperatively protect platinum-resistant ovarian cancer cells from apoptosis. Despite BH3-mimetics represent promising drugs to target Bcl-xL, anti-Mcl-1 strategies are still in pre-clinical studies and required new investigations. Calcium is a universal second messenger and dysregulation of calcium signal is often observed during carcinogenesis. As change in ...
Source: Apoptosis - January 28, 2015 Category: Molecular Biology Source Type: research

How apoptotic β-cells direct immune response to tolerance or to autoimmune diabetes: a review
Abstract Type 1 diabetes (T1D) is a metabolic disease that results from the autoimmune attack against insulin-producing β-cells in the pancreatic islets of Langerhans. Currently, there is no treatment to restore endogenous insulin secretion in patients with autoimmune diabetes. In the last years, the development of new therapies to induce long-term tolerance has been an important medical health challenge. Apoptosis is a physiological mechanism that contributes to the maintenance of immune tolerance. Apoptotic cells are a source of autoantigens that induce tolerance after their removal by antigen presenting ce...
Source: Apoptosis - January 22, 2015 Category: Molecular Biology Source Type: research

Activation of NOD1 by DAP contributes to myocardial ischemia/reperfusion injury via multiple signaling pathways
Abstract NOD1 is a member of nucleotide-binding oligomerization domain-like receptors family that participates in many inflammatory processes. Previous studies demonstrated that NOD1 plays an important role in inflammatory cardiovascular diseases. However, its role in myocardial ischemia/reperfusion (I/R) injury remains unknown. The present study investigate whether NOD1 is involved in the pathogenesis of mouse myocardial I/R injury and the underlying mechanisms. Administration of NOD1 ligand (DAP) significantly enhanced myocardial I/R injury, as demonstrated by increased infarct size, the number of TUNEL-posi...
Source: Apoptosis - January 22, 2015 Category: Molecular Biology Source Type: research

Exposure to the complement C5b-9 complex sensitizes 661W photoreceptor cells to both apoptosis and necroptosis
Abstract The loss of photoreceptors is the defining characteristic of many retinal degenerative diseases, but the mechanisms that regulate photoreceptor cell death are not fully understood. Here we have used the 661W cone photoreceptor cell line to ask whether exposure to the terminal complement complex C5b-9 induces cell death and/or modulates the sensitivity of these cells to other cellular stressors. 661W cone photoreceptors were exposed to complete normal human serum following antibody blockade of CD59. Apoptosis induction was assessed morphologically, by flow cytometry, and on western blotting by probing for ...
Source: Apoptosis - January 21, 2015 Category: Molecular Biology Source Type: research

Liver-specific Fas silencing prevents galactosamine/lipopolysaccharide-induced liver injury
Abstract Acute liver failure (ALF) is a life threatening disease for which only few treatment options exist. The molecular pathways of disease progression are not well defined, but the death receptor Fas (CD95/Apo-1) appears to play a pivotal role in hepatocyte cell death and the development of ALF. Here, we explored posttranscriptional gene silencing of Fas by RNAi to inhibit pathophysiological gene expression. For targeting Fas expression in mice, Fas siRNA was formulated with the liver-specific siRNA delivery system DBTC. Treatment of mice with DBTC/siRNAFas reduced Fas expression in the liver, but not in the&n...
Source: Apoptosis - January 20, 2015 Category: Molecular Biology Source Type: research

Functional, morphological, and apoptotic alterations in skeletal muscle of ARC deficient mice
Abstract Apoptotic signaling plays an important role in the development and maintenance of healthy skeletal muscle. However, dysregulation of apoptotic signals in skeletal muscle is associated with atrophy and loss of function. Apoptosis repressor with caspase recruitment domain (ARC) is a potent anti-apoptotic protein that is highly expressed in skeletal muscle; however, its role in this tissue has yet to be elucidated. To investigate whether ARC deficiency has morphological, functional, and apoptotic consequences, skeletal muscle from 18 week-old wild-type and ARC knockout (KO) mice was studied. In red musc...
Source: Apoptosis - January 18, 2015 Category: Molecular Biology Source Type: research

Evaluation of a dansyl-based amino acid DNSBA as an imaging probe for apoptosis detection
In conclusion, DNSBA cellular imaging is useful for the early assessment of treatment-induced apoptosis, and thus may act as a substitute for Annexin V for assessing treatment response. (Source: Apoptosis)
Source: Apoptosis - January 18, 2015 Category: Molecular Biology Source Type: research

Letter to the Editor: Caspase cleavage sites in the human proteome: CaspDB, a database of predicted substrates
(Source: Apoptosis)
Source: Apoptosis - January 13, 2015 Category: Molecular Biology Source Type: research

S-nitrosylation of XIAP at Cys 213 of BIR2 domain impairs XIAP’s anti-caspase 3 activity and anti-apoptotic function
In this study, we report that cysteine (Cys) 90, Cys 213 and Cys 327 can be specifically S-nitrosylated by NO. We found that mutations of Cys 90 and Cys 327 affect the normal structure of XIAP. More importantly, we found that S-nitrosylation of XIAP Cys 213 impairs the anti-caspase 3 and anti-apoptotic function of XIAP that we observed in our previous study. (Source: Apoptosis)
Source: Apoptosis - January 12, 2015 Category: Molecular Biology Source Type: research

Chronic hepatitis C virus infection triggers spontaneous differential expression of biosignatures associated with T cell exhaustion and apoptosis signaling in peripheral blood mononucleocytes
Abstract Persistent hepatitis C virus (HCV) infection appears to trigger the onset of immune exhaustion to potentially assist viral persistence in the host, eventually leading to hepatocellular carcinoma. The role of HCV on the spontaneous expression of markers suggestive of immune exhaustion and spontaneous apoptosis in immune cells of chronic HCV (CHC) disease largely remain elusive. We investigated the peripheral blood mononuclear cells of CHC patients to determine the spontaneous recruitment of cellular reactive oxygen species (cROS), immunoregulatory and exhaustion markers relative to healthy controls. Using ...
Source: Apoptosis - January 11, 2015 Category: Molecular Biology Source Type: research

17β-Estradiol protects against apoptosis induced by interleukin-1β in rat nucleus pulposus cells by down-regulating MMP-3 and MMP-13
Abstract In our previous study, 17β-estradiol was proved to protect rat annulus fibrosus cells against apoptosis induced by interleukin-1β (IL-1β). However, whether 17β-estradiol has protective effect on rat nucleus pulposus cells remains unclear. The purpose of this study was to further explore the effects of 17β-estradiol on rat nucleus pulposus cells based on IL-1β-induced apoptosis. TUNEL assay and Annexin V/PI double staining were used to detect apoptosis and revealed that IL-1β induced notable apoptosis, which was reversed by 17β-estradiol. Meanwhile, cell viability an...
Source: Apoptosis - January 9, 2015 Category: Molecular Biology Source Type: research

Avian reovirus S1133-induced apoptosis is associated with Bip/GRP79-mediated Bim translocation to the endoplasmic reticulum
In this study the mechanism of avian reovirus (ARV) S1133-induced pathogenesis was investigated, with a focus on the contribution of ER stress to apoptosis. Our results showed that upregulation of the ER stress response protein, as well as caspase-3 activation, occurred in ARV S1133-infected cultured cells and in SPF White Leghorn chicks organs. Upon infection, Bim was translocated specifically to the ER, but not mitochondria, in the middle to late infectious stages. In addition, ARV S1133 induced JNK phosphorylation and promoted JNK–Bim complex formation, which correlated with the Bim translocation and apoptosis ind...
Source: Apoptosis - January 9, 2015 Category: Molecular Biology Source Type: research

Determinants of eosinophil survival and apoptotic cell death
This article discusses the fundamental role of the extracellular and intracellular molecules that initiate and control survival decisions by human Eos and highlights the role of the cis–trans isomerase, Pin1 in controlling these processes. (Source: Apoptosis)
Source: Apoptosis - January 7, 2015 Category: Molecular Biology Source Type: research

Toll/interleukin-1 receptor (TIR) domain-mediated cellular signaling pathways
Abstract Innate immunity, which is the first line of host defense against invading microbial pathogens in multicellular organisms, occurs through germline-encoded pattern-recognition receptors. The Toll-like receptor/Interleukin (IL)-1 receptor (TLR/IL-1R) superfamily comprises proteins that contain the phylogenetically conserved Toll/IL-1 receptor (TIR) domain, which is responsible for the propagation of downstream signaling through recruitment of TIR domain containing cytosolic adaptor proteins such as MyD88, TIRAP/MAL, TRIF, TRAM and SARM. These interactions activate transcription factors that regulate the expr...
Source: Apoptosis - January 7, 2015 Category: Molecular Biology Source Type: research

Tissue inhibitor of metalloproteinase-3 (TIMP3) promotes endothelial apoptosis via a caspase-independent mechanism
In this study, we examined the molecular mechanisms of TIMP3-mediated apoptosis in endothelial cells. We have previously demonstrated that mice developed smaller tumors with decreased vascularity when injected with breast carcinoma cells overexpressing TIMP3, than with control breast carcinoma cells. TIMP3 overexpression resulted in increased apoptosis in human breast carcinoma (MDA-MB435) in vivo but not in vitro. However, TIMP3 could induce apoptosis in ECs in vitro. The apoptotic activity of TIMP3 in ECs appears to be independent of MMP inhibitory activity. Furthermore, the equivalent expression of functional TIMP3 prom...
Source: Apoptosis - January 4, 2015 Category: Molecular Biology Source Type: research

Thy28 protects against anti-CD3-mediated thymic cell death in vivo
Abstract Apoptotic cell death plays a pivotal role in the development and/or maintenance of several tissues including thymus. Deregulated thymic cell death is associated with autoimmune diseases including experimental autoimmune encephalomyelitis (EAE), a prototype murine model for analysis of human multiple sclerosis. Because Thy28 expression is modulated during thymocyte development, we tested whether Thy28 affects induction of EAE as effectively as antigen-induced thymocyte deletion using Thy28 transgenic (TG) mice. Thy28 TG mice showed partial resistance to anti-CD3 monoclonal antibody (mAb)-induced thymic cel...
Source: Apoptosis - December 29, 2014 Category: Molecular Biology Source Type: research

Mycobacterium tuberculosis 38-kDa antigen induces endoplasmic reticulum stress-mediated apoptosis via toll-like receptor 2/4
In conclusion, MCPIP is important for host defense mechanisms in mycobacterial pathogenesis. (Source: Apoptosis)
Source: Apoptosis - December 28, 2014 Category: Molecular Biology Source Type: research

5-HT 2B receptor blockade attenuates β-adrenergic receptor-stimulated myocardial remodeling in rats via inhibiting apoptosis: role of MAPKs and HSPs
In conclusion, inhibition of apoptosis via modulation of MAPKs/HSPs is essential for 5-HT2BR blockade mediated cardioprotective effect. (Source: Apoptosis)
Source: Apoptosis - December 28, 2014 Category: Molecular Biology Source Type: research

Myofibrillogenesis regulator-1 attenuated hypoxia/reoxygenation-induced apoptosis by inhibiting the PERK/Nrf2 pathway in neonatal rat cardiomyocytes
Abstract The purpose of this study was to investigate the role of myofibrillogenesis regulator-1 (MR-1) in cardiomyocyte apoptosis induced by hypoxia/reoxygenation (H/R), through protein kinase R-like ER kinase (PERK)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. To address this aim, an H/R model of neonatal rat cardiomyocytes was used. MR-1 was overexpressed using an adenoviral vector system and knocked down using MR-1 specific siRNA. Apoptosis was assessed by using Annexin V/PI double staining, terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling assay, and the Bcl-2/Bax rat...
Source: Apoptosis - December 26, 2014 Category: Molecular Biology Source Type: research

Gamma-linolenic acid inhibits hepatic PAI-1 expression by inhibiting p38 MAPK-dependent activator protein and mitochondria-mediated apoptosis pathway
Abstract Fibrosis is induced by the excessive and abnormal deposition of extracellular matrix (ECM) with various growth factors in tissues. Transforming growth factor beta 1 (TGF-β1), plays a role in inducing apoptosis, modulates fibrosis, and ECM accumulation. Plasminogen activator inhibitor 1 (PAI-1) plays an important role in the development hepatic fibrosis. The overexpression of PAI-1 induces ECM accumulation, the main hallmark of chronic liver diseases. Death of hepatocytes is a characteristic feature of chronic liver disease due to various causes. The TGF-β1-mediated apoptotic pathway is regarded ...
Source: Apoptosis - December 23, 2014 Category: Molecular Biology Source Type: research

p27 kip1 overexpression regulates VEGF expression, cell proliferation and apoptosis in cell culture from eutopic endometrium of women with endometriosis
Abstract We hypothesized that p27kip1 overexpression can regulate endometriosis cell proliferation, apoptosis and vascular endothelial growth factor (VEGF) expression in the endometrium. The overexpression of p27kip1 was obtained by transduction of p27kip1 in primary cultures of endometrium obtained from women with endometriosis tissue with gene therapy technology. First generation bicistronic adenovirus: AdCMVhp27IRESEGFP (Adp27) and AdCMVNull (AdNull) were engineered in order to induce p27kip1 expression in endometrial cells primary culture. The effect of p27kip1 overexpression was elucidated through the cell pr...
Source: Apoptosis - December 23, 2014 Category: Molecular Biology Source Type: research

Hijacking of death receptor signaling by bacterial pathogen effectors
Abstract Death receptors such as Tumor necrosis factor receptor 1, FAS and TNF-associated apoptosis-inducing ligand-R1/2 play a major role in counteracting with bacterial pathogen infection through regulation of inflammation and programmed cell death. The highly regulated death receptor signaling is frequently targeted by gram-negative bacterial pathogens such as Salmonella, Shigella, enteropathogenic Escherichia coli and enterohamorrhagic Escherichia coli, which harbor a conserved type III secretion system that delivers a repertoire of effector proteins to manipulate host signal transductions for their own benefi...
Source: Apoptosis - December 21, 2014 Category: Molecular Biology Source Type: research

FOXO3-mediated up-regulation of Bim contributes to rhein-induced cancer cell apoptosis
Abstract The anthraquinone compound rhein is a natural agent in the traditional Chinese medicine rhubarb. Preclinical studies demonstrate that rhein has anticancer activity. Treatment of a variety of cancer cells with rhein may induce apoptosis. Here, we report that rhein induces atypical unfolded protein response in breast cancer MCF-7 cells and hepatoma HepG2 cells. Rhein induces CHOP expression, eIF2α phosphorylation and caspase cleavage, while it does not induce glucose-regulated protein 78 (GRP78) expression in both MCF-7 and HepG2 cells. Meanwhile, rhein inhibits thapsigargin-induced GRP78 expression a...
Source: Apoptosis - December 12, 2014 Category: Molecular Biology Source Type: research

Structural insight into CIDE domains: the Janus face of CIDEs
Abstract Cell-death inducing DFF45-like effect domain (CIDE domain) is a protein interaction module that was initially found in DNA fragmentation factor (DFF) proteins DFF40 and DFF45. Several other CIDE-containing proteins, CIDE-A, CIDE-B, and CIDE-3, have since been identified in humans. Although the main function of these proteins is associated with apoptosis, recent studies have identified roles of CIDE-containing proteins in energy metabolism, especially involvement in control of the size of lipid droplets. Because CIDE-containing proteins perform critical tasks in apoptosis and energy metabolism and have bee...
Source: Apoptosis - December 9, 2014 Category: Molecular Biology Source Type: research

An updated view on the structure and function of PYRIN domains
Abstract The PYRIN domain (PYD) is a protein–protein interaction domain, which belongs to the death domain fold (DDF) superfamily. It is best known for its signaling function in innate immune responses and particularly in the assembly of inflammasomes, which are large protein complexes that allow the induced proximity-mediated activation of caspase-1 and subsequently the release of pro-inflammatory cytokines. The molecular mechanism of inflammasome assembly was only recently elucidated and specifically requires PYD oligomerization. Here we discuss the recent advances in our understanding of PYD signaling and...
Source: Apoptosis - December 1, 2014 Category: Molecular Biology Source Type: research

Neuroprotective effects of three different sizes nanochelating based nano complexes in MPP(+) induced neurotoxicity
Abstract Parkinson’s disease (PD) is the world’s second most common dementia, which the drugs available for its treatment have not had effects beyond slowing the disease process. Recently nanotechnology has induced the chance for designing and manufacturing new medicines for neurodegenerative disease. It is demonstrated that by tuning the size of a nanoparticle, the physiological effect of the nanoparticle can be controlled. Using novel nanochelating technology, three nano complexes: Pas (150 nm), Paf (100 nm) and Pac (40 nm) were designed and in the present study their neuroprotective e...
Source: Apoptosis - December 1, 2014 Category: Molecular Biology Source Type: research

Structure and function of Toll/interleukin-1 receptor/resistance protein (TIR) domains
Abstract The Toll/interleukin-1 receptor/resistance protein (TIR) domain is a protein–protein interaction domain consisting of 125–200 residues, widely distributed in animals, plants and bacteria but absent from fungi, archea and viruses. In plants and animals, these domains are found in proteins with functions in innate immune pathways, while in bacteria, some TIR domain-containing proteins interfere with the innate immune pathways in the host. TIR domains function as protein scaffolds, mostly involving self-association and homotypic interactions with other TIR domains. In the last 15 years, the ...
Source: Apoptosis - December 1, 2014 Category: Molecular Biology Source Type: research

Death effecter domain for the assembly of death-inducing signaling complex
Abstract Death-inducing signaling complex (DISC) is a platform for the activation of initiator caspase in extrinsic apoptosis. Assembly of DISC is accomplished by two different types of homotypic interaction: one is between death domains (DDs) of a death receptor and FADD, and the other is between death effecter domains (DEDs) of FADD, procaspase-8/-10 and cFLIP. Recent biochemical investigations on the stoichiometry of DISC have revealed that single-DED-containing FADD exists in DISC in a substantially lower abundance than the sum of tandem-DEDs-containing components that are procaspase-8 and cFLIP. In addition, ...
Source: Apoptosis - December 1, 2014 Category: Molecular Biology Source Type: research

Structural basis of cell apoptosis and necrosis in TNFR signaling
Abstract The tumor necrosis factor receptors (TNFRs) play essential roles in innate and adaptive immunity. Depending on conditions, TNFR induces multiple cell fates including cell survival, cell apoptosis, and cell programmed necrosis. Here, we review recent progress in structural studies of the TNFR signaling pathway. The structural basis for the high order signal complexes, including the DISC, ripoptosome, necrosome, and RIP3/MLKL complex, may provide novel insights for understanding the biophysical principles of cell signaling cascades. (Source: Apoptosis)
Source: Apoptosis - December 1, 2014 Category: Molecular Biology Source Type: research

Pro-apoptotic gene regulation and its activation by gamma-irradiation in the Caribbean fruit fly, Anastrepha suspensa
In this study, we determined the developmental profiles of Asrpr and Ashid transcripts during embryogenesis and in embryos exposed to γ-irradiation. Transcript levels of both genes determined by qRT-PCR were low throughout embryogenesis, with strong Ashid expression occurring during early to mid-embryogenesis and Asrpr expression peaking in late embryogenesis. This correlated to acridine orange stained apoptotic cells first appearing at 17 h and increasing over time. However, when irradiated at 16 h post-oviposition embryos exhibited significant levels of apoptosis consistent with strong induction of Asrpr ...
Source: Apoptosis - November 30, 2014 Category: Molecular Biology Source Type: research

Apoptosis imaging studies in various animal models using radio-iodinated peptide
In this study, we radiolabeled the recently identified histone H1 targeting peptide (ApoPep-1) and evaluated its potential as a new apoptosis imaging agent in various animal models. ApoPep-1 (CQRPPR) was synthesized, and an extra tyrosine residue was added to its N-terminal end for radiolabeling. This peptide was radiolabeled with 124I and 131I and was tested for its serum stability. Surgery- and drug-induced apoptotic rat models were prepared for apoptosis evaluation, and PET imaging was performed. Doxorubicin was used for xenograft tumor treatment in mice, and the induced apoptosis was studied. Tumor metabolism and proli...
Source: Apoptosis - November 28, 2014 Category: Molecular Biology Source Type: research

mTOR ATP-competitive inhibitor INK128 inhibits neuroblastoma growth via blocking mTORC signaling
In conclusion, we have shown that INK128-mediated mTOR inhibition possessed substantial antitumor activity and could significantly increase the sensitivity of neuroblastoma cells to Dox therapy. Taken together, our results indicate that using INK128 can provide additional efficacy to current chemotherapeutic regimens and represent a new paradigm in restoring drug sensitivity in neuroblastoma. (Source: Apoptosis)
Source: Apoptosis - November 26, 2014 Category: Molecular Biology Source Type: research

The versatile roles of CARDs in regulating apoptosis, inflammation, and NF-κB signaling
Abstract CARD subfamily is the second largest subfamily in the DD superfamily that plays important roles in regulating various signaling pathways, including but not limited to NF-kB activation signaling, apoptosis signaling and inflammatory signaling. The CARD subfamily contains 33 human CARD-containing proteins, regulating the assembly of many signaling complexes, including apoptosome, inflammsome, nodosome, the CBM complex, PIDDosome, the TRAF2 complex, and the MAVS signalosome, by homotypic CARD–CARD interactions. The mechanism of how CARDs find the right binding partner to form a specific complex remains...
Source: Apoptosis - November 24, 2014 Category: Molecular Biology Source Type: research

MiR-218-targeting-Bmi-1 mediates the suppressive effect of 1,6,7-trihydroxyxanthone on liver cancer cells
In conclusion, THA might be a potential anti-cancer drug candidate, at least in part, through the activation of miR-218 and suppression of Bmi-1 expression. (Source: Apoptosis)
Source: Apoptosis - November 21, 2014 Category: Molecular Biology Source Type: research

TSPO ligand residence time influences human glioblastoma multiforme cell death/life balance
Abstract Ligands addressed to the mitochondrial Translocator Protein (TSPO) have been suggested as cell death/life and steroidogenesis modulators. Thus, TSPO ligands have been proposed as drug candidates in several diseases; nevertheless, a correlation between their binding affinity and in vitro efficacy has not been demonstrated yet, questioning the specificity of the observed effects. Since drug-target residence time is an emerging parameter able to influence drug pharmacological features, herein, the interaction between TSPO and irDE-MPIGA, a covalent TSPO ligand, was investigated in order to explore TSPO contr...
Source: Apoptosis - November 20, 2014 Category: Molecular Biology Source Type: research

The Bcl-2 family: structures, interactions and targets for drug discovery
Abstract Two phylogenetically and structurally distinct groups of proteins regulate stress induced intrinsic apoptosis, the programmed disassembly of cells. Together they form the B cell lymphoma-2 (Bcl-2) family. Bcl-2 proteins appeared early in metazoan evolution and are identified by the presence of up to four short conserved sequence blocks known as Bcl-2 homology (BH) motifs, or domains. The simple BH3-only proteins bear only a BH3-motif and are intrinsically disordered proteins and antagonize or activate the other group, the multi-motif Bcl-2 proteins that have up to four BH motifs, BH1-BH4. Multi-motif Bcl-...
Source: Apoptosis - November 15, 2014 Category: Molecular Biology Source Type: research