Overcoming chemotherapy drug resistance by targeting inhibitors of apoptosis proteins (IAPs)
AbstractInhibitors of apoptosis (IAPs) are a family of proteins that play a significant role in the control of programmed cell death (PCD). PCD is essential to maintain healthy cell turnover within tissue but also to fight disease or infection. Uninhibited, IAPs can suppress apoptosis and promote cell cycle progression. Therefore, it is unsurprising that cancer cells demonstrate significantly elevated expression levels of IAPs, resulting in improved cell survival, enhanced tumor growth and subsequent metastasis. Therapies to target IAPs in cancer has garnered substantial scientific interest and as resistance to anti-cancer...
Source: Apoptosis - April 19, 2017 Category: Molecular Biology Source Type: research

Role of glycogen synthase kinase following myocardial infarction and ischemia –reperfusion
AbstractGlycogen synthase kinase-3 beta (GSK3 β) is principally is a glycogen synthase phosphorylating enzyme that is well known for its role in muscle metabolism. GSK3β is a serine/threonine protein Kinase, which is responsible for several essential roles in mammalian cells. This enzyme is implicated in the pathophysiology of many conditions involved in homeostasis and cellular immigration. GSK3β is involved in several pathways leading to neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Increasing evidence has shown the potential importance of GSK3β in ischemi...
Source: Apoptosis - April 18, 2017 Category: Molecular Biology Source Type: research

Retraction Note to: Advanced oxidation protein products induce chondrocyte death through a redox-dependent, poly(ADP-ribose) polymerase-1-mediated pathway
(Source: Apoptosis)
Source: Apoptosis - April 18, 2017 Category: Molecular Biology Source Type: research

Alcohol and thiamine deficiency trigger differential mitochondrial transition pore opening mediating cellular death
This study indicates two different mitochondria pathways regulating cellular death: The first mechanism may engage alcohol which activates the c-subunit ring of the F0-ATP synthase to form MPT pore-dependent apoptosis; following the second mechanism, TD activates CyP-D translocation from mitochondrial matrix towards the mitochondrial inner membrane to form MPT pore-dependent necrosis. These studies shed light upon molecular and cellular mechanisms underlying apoptosis and necrosis in developemental brain disorders related to alcohol and thiamine deficiency, in hopes of developing new therapeutic strategies for FAS medicati...
Source: Apoptosis - April 17, 2017 Category: Molecular Biology Source Type: research

Pro-apoptotic signaling induced by Retinoic acid and dsRNA is under the control of Interferon Regulatory Factor-3 in breast cancer cells
AbstractBreast cancer is one of the most lethal malignancies for women. Retinoic acid (RA) and double-stranded RNA (dsRNA) are considered signaling molecules with potential anticancer activity. RA, co-administered with the dsRNA mimic polyinosinic –polycytidylic acid (poly(I:C)), synergizes to induce a TRAIL (Tumor-Necrosis-Factor Related Apoptosis-Inducing Ligand)- dependent apoptotic program in breast cancer cells. Here, we report that RA/poly(I:C) co-treatment, synergically, induce the activation of Interferon Regulatory Factor-3 (IRF3) in breast cancer cells. IRF3 activation is mediated by a member of the pathoge...
Source: Apoptosis - April 13, 2017 Category: Molecular Biology Source Type: research

Study on the apoptosis mediated by cytochrome c and factors that affect the activation of bovine longissimus muscle during postmortem aging
This study investigates whether bovine longissimus muscle cell apoptosis occurs during postmortem aging and whether apoptosis is dependent on the mitochondria pathway. This study also determines the apoptosis process mediated by cytochrome c after its release from mitochondria and the factors that affect the activation processes. Results indicate that apoptotic nuclei were detected at 12  h postmortem. Cytochrome c release from the mitochondria to the cytoplasm activated the caspase-9 and caspase-3 at early postmortem aging and the activation of caspase-9 occurs before the activation of caspase-3. The pH level decreas...
Source: Apoptosis - April 12, 2017 Category: Molecular Biology Source Type: research

Novel Triazole linked 2-phenyl benzoxazole derivatives induce apoptosis by inhibiting miR-2, miR-13 and miR-14 function in Drosophila melanogaster
In this study, we have identified novel Triazole linked 2-phenyl benzoxazole derivatives (13j and 13h) as a negative regulator of apoptosis inhibiting micro RNAs (miR-2, miR-13 and miR-14) in a well established in vivo modelDrosophila melanogaster where the process of apoptosis is very similar to human apoptosis. These compounds inhibitmiR-2, miR-13 andmiR-14 activity at their target sites, which induce an increased caspase activity, and in turn influence the caspase dependent apoptotic pathway. These two compounds also increase the mitochondrial reactive oxygen species  (ROS) level to trigger apoptotic cell death. (Source: Apoptosis)
Source: Apoptosis - April 11, 2017 Category: Molecular Biology Source Type: research

PERK signalling pathway mediates single prolonged stress-induced dysfunction of medial prefrontal cortex neurons
AbstractPost-traumatic stress disorder (PTSD) is characterized with abnormal learning and memory. Impairments in learning and memory are closely associated with apoptosis in the medial prefrontal cortex (mPFC). We previously examined the endoplasmic reticulum (ER) stress was involved in the apoptosis in the mPFC of PTSD. The PERK pathway plays the important role in the ER stress-induced apoptosis. The aim of the present study was to explore the role of PERK pathway in neuronal apoptosis in the mPFC of rat models of PTSD. We used the single prolonged stress (SPS) to mimic PTSD in rats and studied the effects of the PERK pat...
Source: Apoptosis - April 8, 2017 Category: Molecular Biology Source Type: research

Fatty acid synthase regulates the chemosensitivity of breast cancer cells to cisplatin-induced apoptosis
AbstractFatty acid synthase (FASN) is a key enzyme in fat biosynthesis that is over-expressed in advanced breast cancer stages. Cisplatin (CDDP) is a platinum-based drug used in the treatment of certain types of this disease. Although it was shown that FASN inhibition induced apoptosis by enhancing the cytotoxicity of certain drugs in breast cancer, its role in regulating the chemosensitivity of different types of breast cancer cells to CDDP-induced apoptosis is not established yet. Therefore, two different breast cancer cell lines; triple negative breast cancer (TNBC; MDA-MB-231) and triple positive breast cancer (TPBC; B...
Source: Apoptosis - April 6, 2017 Category: Molecular Biology Source Type: research

Relaxin attenuates aristolochic acid induced human tubular epithelial cell apoptosis in vitro by activation of the PI3K/Akt signaling pathway
AbstractAristolochic acid nephropathy remains a leading cause of chronic kidney disease (CKD), however few treatment strategies exist. Emerging evidence has shown that H2 relaxin (RLX) possesses powerful antifibrosis and anti-apoptotic properties, therefore we aimed to investigate whether H2 relaxin  can be employed to reduce AA-induced cell apoptosis. Human proximal tubular epithelial (HK-2) cells exposed to AA-I were treated with or without administration of H2 RLX. Cell viability was examined using the WST-8 assay. Apoptotic morphologic alterations were observed using the Hoechst 33342 stai ning method. Apoptosis w...
Source: Apoptosis - April 6, 2017 Category: Molecular Biology Source Type: research

Notch-4 silencing inhibits prostate cancer growth and EMT via the NF- κB pathway
AbstractEpithelial-mesenchymal transition (EMT) is implicated in the metastasis of human prostate cancer (PCa). Notch signaling has been established as a regulator of EMT. Notch-4 has emerged as a mammary proto-oncogene and a target in several cancers. However, the role and the mechanism of action of Notch-4 in PCa are still unclear. In the present study, we first observed a marked increase in Notch-4 expression in the PCa cell lines DU145, PC3 and LnCAP compared with the non-malignant prostate epithelial cell line RWPE1. Knocking down the expression of Notch-4 suppressed the viability and proliferation in the PCa cell lin...
Source: Apoptosis - April 3, 2017 Category: Molecular Biology Source Type: research

EGCG protects against homocysteine-induced human umbilical vein endothelial cells apoptosis by modulating mitochondrial-dependent apoptotic signaling and PI3K/Akt/eNOS signaling pathways
In conclusion, the present study shows that EGCG prevents Hcy-induced HUVECs apoptosis via modulating mitochondrial apoptotic and PI3K/Akt/eNOS signaling pathways. Furthermore, the results indicate that EGCG is likely to represent a potential therapeutic strategy for atherosclerosis associated with Hyperhomocysteinemia (HHcy). (Source: Apoptosis)
Source: Apoptosis - March 18, 2017 Category: Molecular Biology Source Type: research

Microglia activation contributes to quinolinic acid-induced neuronal excitotoxicity through TNF- α
AbstractIt has been reported that activation of NF- κB is involved in excitotoxicity; however, it is not fully understood how NF-κB contributes to excitotoxicity. The aim of this study is to investigate if NF-κB contributes to quinolinic acid (QA)-mediated excitotoxicity through activation of microglia. In the cultured primary cortical neurons and microglia BV-2 cells, the effects of QA on cell survival, NF-κB expression and cytokines production were investigated. The effects of BV-2-conditioned medium (BCM) on primary cortical neurons were examined. The effects of pyrrolidine dithiocarbamate (PDTC)...
Source: Apoptosis - March 16, 2017 Category: Molecular Biology Source Type: research

Ricolinostat, a selective HDAC6 inhibitor, shows anti-lymphoma cell activity alone and in combination with bendamustine
AbstractHistone deacetylase inhibitors (HDACis) have emerged as a new class of anticancer agents, targeting the biological process including cell cycle and apoptosis. We investigated and explained the anticancer effects of an HDAC6 inhibitor, ricolinostat alone and in combination with bendamustine in lymphoma cell lines. Cell viability was measured by MTT assay. Apoptosis, reactive oxygen species (ROS) generation, Bcl-2 protein expression, cell cycle progression and tubuline expression were determined by flow cytometry. The effects of ricolinostat alone and in combination on the caspases, PI3K/Akt, Bcl-2 pathways, ER stres...
Source: Apoptosis - March 16, 2017 Category: Molecular Biology Source Type: research

A novel non-ATP competitive FGFR1 inhibitor with therapeutic potential on gastric cancer through inhibition of cell proliferation, survival and migration
AbstractFibroblast growth factor receptor 1 (FGFR1), belonging to receptor tyrosine kinases (RTKs), possesses various biological functions. Over-expression of FGFR1 has been observed in multiple human malignancies. Hence, targeting FGFR1 is an attractive prospect for the advancement of cancer treatment options. Here, we present a novel small molecular FGFR1 inhibitor L16H50, which can inhibit FGFR1 kinase in an ATP-independent manner. It potently inhibits FGFR1-mediated signaling in a gastric cancer cell line, resulting in inhibition of cell growth, survival and migration. It also displays an outstanding anti-tumor activit...
Source: Apoptosis - March 16, 2017 Category: Molecular Biology Source Type: research

Changes in membrane lipids drive increased endocytosis following Fas ligation
AbstractOnce activated, some surface receptors promote membrane movements that open new portals of endocytosis, in part to facilitate the internalization of their activated complexes. The prototypic death receptor Fas (CD95/Apo1) promotes a wave of enhanced endocytosis that induces a transient intermixing of endosomes with mitochondria in cells that require mitochondria to amplify death signaling. This initiates a global alteration in membrane traffic that originates from changes in key membrane lipids occurring in the endoplasmic reticulum (ER). We have focused the current study on specific lipid changes occurring early a...
Source: Apoptosis - March 14, 2017 Category: Molecular Biology Source Type: research

RIPK1/RIPK3/MLKL-mediated necroptosis contributes to compression-induced rat nucleus pulposus cells death
AbstractThe aim of this study was to systematically investigate the role of necroptosis in compression-induced rat nucleus pulposus (NP) cells death, as well as explore the underlying mechanisms involved. Rat NP cells underwent various periods of exposure to 1.0  MPa pressure. Cell viability and cell death were quantified by using cell counting kit-8 (CCK-8), and Calcein-AM/propidium iodine (PI) staining respectively. Necroptosis-associated target molecules receptor-interacing protein kinase 1 (RIPK1), phosphorylated RIPK1 (pRIPK1), receptor-interacing pro tein kinase 3 (RIPK3), phosphorylated RIPK3 (pRIPK3) and mixed...
Source: Apoptosis - March 12, 2017 Category: Molecular Biology Source Type: research

CF 3 DODA-Me induces apoptosis, degrades Sp1, and blocks the transformation phase of the blebbishield emergency program
AbstractCancer stem cells are capable of undergoing cellular transformation after commencement of apoptosis through the blebbishield emergency program in a VEGF-VEGFR2-dependent manner. Development of therapeutics targeting the blebbishield emergency program would thus be important in cancer therapy. Specificity protein 1 (Sp1) orchestrates the transcription of both VEGF and VEGFR2; hence, Sp1 could act as a therapeutic target. Here, we demonstrate that CF3DODA-Me induced apoptosis, degraded Sp1, inhibited the expression of multiple drivers of the blebbishield emergency program such as VEGFR2, p70S6K, and N-Myc through act...
Source: Apoptosis - March 10, 2017 Category: Molecular Biology Source Type: research

Taurine ameliorated homocysteine-induced H9C2 cardiomyocyte apoptosis by modulating endoplasmic reticulum stress
This study aimed to evaluate the opposite effects of taurine on Hcy-induced cardiomyocyte apoptosis and their underlying mechanisms. Our results demonstrated that low-dose or short-term Hcy treatment increased the expression of glucose-regulated protein 78 (GRP78) and activated protein kinase RNA-like ER kinase (PERK), inositol-requiring enzyme 1 (IRE1), and activating transcription factor 6 (ATF6), which in turn prevented apoptotic cell death. High-dose Hcy or prolonged Hcy treatment duration significantly up-regulated levels of C/EBP homologous protein (CHOP), cleaved caspase-12, p-c-JunN-terminal kinase (JNK), and then ...
Source: Apoptosis - February 21, 2017 Category: Molecular Biology Source Type: research

Exposure to chronic hyperglycemic conditions results in Ras-related C3 botulinum toxin substrate 1 (Rac1)-mediated activation of p53 and ATM kinase in pancreatic β-cells
In conclusion, these data indicate that sustained activation of Rac1-p38MAPK signaling axis leads to activation of p53 leading to β-cell dysfunction under the d uress of chronic hyperglycemic conditions. (Source: Apoptosis)
Source: Apoptosis - February 20, 2017 Category: Molecular Biology Source Type: research

Anandamide oxidative metabolism-induced endoplasmic reticulum stress and apoptosis
In this study, we aimed to disclose the mechanisms underlying the effects of AEA in human endometrial stromal cell fate, using a human-derived endometrial cell line (St-T1b). We found that AEA has an anti-proliferative activity through a direct effect on cell cycle progression by inducing G2/M arrest. Moreover, high levels of AEA increased COX-2 activity, triggering apoptotic cell death, with loss of mitochondrial membrane potential, induction of caspase -9 and -3/-7 activities, and cleavage of poly (ADP-ribose) polymerase (PARP). In addition, the involvement of intracellular reactive oxygen species (ROS) and endoplasmic r...
Source: Apoptosis - February 19, 2017 Category: Molecular Biology Source Type: research

Ursolic acid-mediated changes in glycolytic pathway promote cytotoxic autophagy and apoptosis in phenotypically different breast cancer cells
AbstractPlant-derived pentacyclic triterpenotids with multiple biological activities are considered as promising candidates for cancer therapy and prevention. However, their mechanisms of action are not fully understood. In the present study, we have analyzed the effects of low dose treatment (5 –20 µM) of ursolic acid (UA) and betulinic acid (BA) on breast cancer cells of different receptor status, namely MCF-7 (ER+, PR+/ −, HER2−), MDA-MB-231 (ER−, PR−, HER2−) and SK-BR-3 (ER−, PR−, HER2+). UA-mediated response was more potent than BA-mediated response. Triterpen...
Source: Apoptosis - February 16, 2017 Category: Molecular Biology Source Type: research

Remifentanil postconditioning ameliorates histone H3 acetylation modification in H9c2 cardiomyoblasts after hypoxia/reoxygenation via attenuating endoplasmic reticulum stress
In this study, an in vitro IRI model was established with H9c2 cardiomyoblasts to investigate the role of histone H3 acetylation and HDAC3 in RPC-induced attenuation of ERS-associated apoptosis. Briefly, H9c2 cardiomyoblasts were randomly subjected to hypoxia/reoxygenation with and without remifentanil administered at the onset of reoxygenation. Results showed that RPC increased cell viability and prevented cell apoptosis (evidenced by CCK-8 cell viability assays and flow cytometry), and these effects were accompanied by lower levels of expression of GRP78, CHOP, cleaved caspase-12, and cleaved caspase-3. RPC also mimicked...
Source: Apoptosis - February 15, 2017 Category: Molecular Biology Source Type: research

Heat shock protein 70 protects cardiomyocytes through suppressing SUMOylation and nucleus translocation of phosphorylated eukaryotic elongation factor 2 during myocardial ischemia and reperfusion
AbstractMyocardial ischemia and reperfusion (MIR) results in cardiomyocyte apoptosis with severe outcomes, which blocks cardiac tissue recovering from myocardial ischemia diseases. Heat shock protein 70 (HSP70) is one of protective molecule chaperones which could regulate the nucleus translocation of other proteins. In addition, eukaryotic elongation factor 2 (eEF2), which modulates protein translation process, is vital to the recovery of heart during MIR. However, the relationship between HSP70 and eEF2 and its effects on MIR are unclear. The expression and relationship between HSP70 and eEF2 is confirmed by western blot,...
Source: Apoptosis - February 14, 2017 Category: Molecular Biology Source Type: research

Apoptosis induced by a snake venom metalloproteinase from Bothrops alternatus venom in C2C12 muscle cells
In conclusion, our results suggest that the absence of appropriate extracellular matrix contacts triggers anoikis. Therefore, this is the first report that demonstrated the mechanism of programmed cell death triggered by baltergin, a PIII metalloprotease isolated fromBothrops alternatus venom, in a myoblast cell line. (Source: Apoptosis)
Source: Apoptosis - February 14, 2017 Category: Molecular Biology Source Type: research

Caspase-3 and caspase-8 expression in breast cancer: caspase-3 is associated with survival
AbstractImpaired apoptosis is one of the hallmarks of cancer. Caspase-3 and -8 are key regulators of the apoptotic response and have been shown to interact with the calpain family, a group of cysteine proteases, during tumorigenesis. The current study sought to investigate the prognostic potential of caspase-3 and -8 in breast cancer, as well as the prognostic value of combinatorial caspase and calpain expression. A large cohort (n  = 1902) of early stage invasive breast cancer patients was used to explore the expression of caspase-3 and -8. Protein expression was examined using standard immunohistochemistry ...
Source: Apoptosis - February 14, 2017 Category: Molecular Biology Source Type: research

Quercetin induces protective autophagy and apoptosis through ER stress via the p-STAT3/Bcl-2 axis in ovarian cancer
AbstractQuercetin (3,3 ′,4′,5,7-pentahydroxyflavone, Qu) is a promising cancer chemo-preventive agent for various cancers because it inhibits disease progression and promotes apoptotic cell death. In our previous study, we demonstrated that Qu could evoke ER stress to enhance drug cytotoxicity in ovarian cancer (OC). However, Qu-induced ER stress in OC is still poorly understood. Here, we demonstrated that Qu evoked ER stress to involve in mitochondria apoptosis pathway via the p-STAT3/Bcl-2 axis in OC cell lines and in primary OC cells. Unexpectedly, inhibition of ER stress did not reverse Qu-induced cell deat...
Source: Apoptosis - February 9, 2017 Category: Molecular Biology Source Type: research

Activation of Na + -K + -ATPase with DRm217 attenuates oxidative stress-induced myocardial cell injury via closing Na + -K + -ATPase/Src/Ros amplifier
AbstractReduced Na+-K+-ATPase activity has close relationship with cardiomyocyte death. Reactive oxygen species (ROS) also plays an important role in cardiac cell damage. It has been proved that Na+-K+-ATPase and ROS form a feed-forward amplifier. The aim of this study was to explore whether DRm217, a proved Na+/K+-ATPase ’s DR-region specific monoclonal antibody and direct activator, could disrupt Na+-K+-ATPase/ROS amplifier and protect cardiac cells from ROS-induced injury. We found that DRm217 protected myocardial cells against hydrogen peroxide (H2O2)-induced cardiac cell injury and mitochondrial dysfunction. DRm...
Source: Apoptosis - February 7, 2017 Category: Molecular Biology Source Type: research

Centchroman induces redox-dependent apoptosis and cell-cycle arrest in human endometrial cancer cells
This study focuses on the basis of antineoplasticity of CC by blocking the targets involved in the cell cycle, survival and apoptosis in endometrial cancer cells. Ishikawa Human Endometrial Cancer Cells were cultured under estrogen deprived medium, exposed to CC and analyzed for proliferation and apoptosis. Additionally, we also analyzed oxidative stress induced by CC. Cell viability studies confirmed the IC50 of CC in Ishikawa cells to be 20  µM after 48 h treatment. CC arrests the cells in G0/G1 phase through cyclin D1 and cyclin E mediated pathways. Phosphatidylserine externalization, nuclear morphology ...
Source: Apoptosis - February 6, 2017 Category: Molecular Biology Source Type: research

Propofol attenuates H 2 O 2 -induced oxidative stress and apoptosis via the mitochondria- and ER-medicated pathways in neonatal rat cardiomyocytes
AbstractPrevious studies have shown that propofol, an intravenous anesthetic commonly used in clinical practice, protects the myocardium from injury. Mitochondria- and endoplasmic reticulum (ER)-mediated oxidative stress and apoptosis are two important signaling pathways involved in myocardial injury and protection. The present study aimed to test the hypothesis that propofol could exert a cardio-protective effect via the above two pathways. Cultured neonatal rat cardiomyocytes were treated with culture medium (control group), H2O2 at 500  μM (H2O2 group), propofol at 50  μM (propofol group), and H2O2 plus ...
Source: Apoptosis - February 6, 2017 Category: Molecular Biology Source Type: research

Surfactant protein D delays Fas- and TRAIL-mediated extrinsic pathway of apoptosis in T cells
In this study we aimed to determine the effects of SP-D on Jurkat T cells and human T cells dying by apoptosis. Here we show that SP-D binds to Jurkat T cells and delays the progression of Fas (CD95)-Fas ligand and TRAIL –TRAIL receptor induced, but not TNF–TNF receptor-mediated apoptosis. SP-D exerts its effects by reducing the activation of initiator caspase-8 and executioner caspase-3. SP-D also delays the surface exposure of phosphatidylserine. The effect of SP-D was ablated by the presence of caspase-8 inhi bitor, but not by intrinsic pathway inhibitors. The binding ability of SP-D to dying cells decreases...
Source: Apoptosis - February 5, 2017 Category: Molecular Biology Source Type: research

Synergy of 2-deoxy- d -glucose combined with berberine in inducing the lysosome/autophagy and transglutaminase activation-facilitated apoptosis
AbstractUtilizing a variety of flow cytometric methods evidence was obtained indicating that a combination of the glucose analog 2-deoxy-d-glucose (2-dG) and the plant alkaloid berberine (BRB) produces synergistic effect in the induction of apoptosis in human lymphoblastoid TK6 cells. The synergistic effect is seen at concentrations of the drugs at which each of them alone shows no cytotoxicity at all. The data suggest that the combination of these drugs, which are known in terms of their overall toxicity, side effects and pharmacokinetics may be considered for further studies as chemopreventive and cancer treatment modali...
Source: Apoptosis - January 31, 2017 Category: Molecular Biology Source Type: research

Transcriptional control of apoptotic cell clearance by macrophage nuclear receptors
AbstractApoptotic cell clearance by macrophages is key for normal tissue development and homeostasis. Nuclear receptors, such as peroxisome proliferator activated receptors (PPARs), liver X receptor (LXR), retinoic acid receptor (RAR), retinoid X receptor (RXR) and glucocorticoid receptor (GR) orchestrate this vital process. The underlying mechanism involves the transcriptional control of key genes of apoptotic cell recognition and internalization, such asCd36, Mertk, Axl, C1qa, Tgm2, Abca1. In addition, apoptotic cell uptake leads to M2 activation of macrophages, and this process is also controlled at the gene transcripti...
Source: Apoptosis - January 31, 2017 Category: Molecular Biology Source Type: research

Cylindrospermopsin induces biochemical changes leading to programmed cell death in plants
AbstractIn the present study we provide cytological and biochemical evidence that the cyanotoxin cylindrospermopsin (CYN) induces programmed cell death (PCD) symptoms in two model vascular plants: the dicot white mustard (Sinapis alba) and the monocot common reed (Phragmites australis). Cytological data include chromatin fragmentation and the increase of the ratio of TUNEL-positive cells in roots, the latter being detected in both model systems studied. The strongest biochemical evidence is the elevation of the activity of several single-stranded DNA preferring nucleases-among them enzymes active at both acidic and alkalin...
Source: Apoptosis - January 31, 2017 Category: Molecular Biology Source Type: research

Myc inhibits JNK-mediated cell death in vivo
AbstractThe proto-oncogene Myc is well known for its roles in promoting cell growth, proliferation and apoptosis. However, in this study, we found from a genetic screen that Myc inhibits, rather than promotes, cell death triggered by c-Jun N-terminal kinase (JNK) signaling inDrosophila. Firstly, expression ofDrosophila Myc (dMyc) suppresses, whereas loss ofdMyc enhances, ectopically activated JNK signaling-induced cell death. Secondly, dMyc impedes physiologically activated JNK pathway-mediated cell death. Thirdly, loss of dMyc triggers JNK pathway activation and JNK-dependent cell death. Finally, the mammaliancMyc gene, w...
Source: Apoptosis - January 31, 2017 Category: Molecular Biology Source Type: research

Defining the morphologic features and products of cell disassembly during apoptosis
(Source: Apoptosis)
Source: Apoptosis - January 18, 2017 Category: Molecular Biology Source Type: research

Synthesis and evaluation of a radiolabeled bis-zinc(II) –cyclen complex as a potential probe for in vivo imaging of cell death
Abstract The exposition of phosphatidylserine (PS) from the cell membrane is associated with most cell death programs (apoptosis, necrosis, autophagy, mitotic catastrophe, etc.), which makes PS an attractive target for overall cell death imaging. To this end, zinc(II) macrocycle coordination complexes with cyclic polyamine units as low-molecular-weight annexin mimics have a selective affinity for biomembrane surfaces enriched with PS, and are therefore useful for detection of cell death. In the present study, a11C-labeled zinc(II) –bis(cyclen) complex (11C-CyclenZn2) was prepared and evaluated as a new positron emi...
Source: Apoptosis - January 12, 2017 Category: Molecular Biology Source Type: research

Caspase dependent and independent mechanisms of apoptosis across gestation in a sheep model of placental insufficiency and intrauterine growth restriction
AbstractIncreased placental apoptosis is a hallmark of intrauterine growth restricted (IUGR). Several molecules have been shown to be involved in the control of apoptosis during this disease. Our objective was to determine the expression of Bcl2, Bax, phospho XIAP, AIF, caspase 3 and 9, and telomerase activity across gestation in an ovine hyperthermia-induced model of IUGR. Pregnant sheep were placed in hyperthermic (HT) conditions to induce IUGR along with age-matched controls. Placental tissues were collected at 55 (early), 95 (mid-gestation) and 130 (near-term) days of gestational age (dGA) to determine the expression o...
Source: Apoptosis - January 11, 2017 Category: Molecular Biology Source Type: research

SIRT2-mediated FOXO3a deacetylation drives its nuclear translocation triggering FasL-induced cell apoptosis during renal ischemia reperfusion
This study is to elucidate the upstream mechanism regulating FasL-induced extrinsic pathway during renal ischemia/reperfusion. Results demonstrated that when SIRT2 was activated by renal ischemia/reperfusion, activated SIRT2 could bind to and deacetylate FOXO3a, promoting FOXO3a nuclear translocation which resulted in an increase of nuclear FOXO3a along with FasL expression and activation of caspase8 and caspase3, triggering cell apoptosis during renal ischemia/reperfusion. The administration of SIRT2 inhibitor A GK2 prior to renal ischemia decreased significantly the number of apoptotic renal tubular cells and alleviated ...
Source: Apoptosis - January 10, 2017 Category: Molecular Biology Source Type: research

Methods to detect apoptotic cell death
AbstractIn concert with the increased understanding that there are many ways for cells to die, several methods have been developed to detect cell death. The classification of cell death posed some difficulties that were overcome by implementing strict selection criteria that should also apply to the detection methods. The selection of assays is based on morphological criteria and distinguishable marks of apoptotic patways. The detection of apoptosis includes methods related to membrane alterations, DNA fragmentation, cytotoxicity and cell proliferation, mitochondrial damage, immunological detection and mechanism based assa...
Source: Apoptosis - December 29, 2016 Category: Molecular Biology Source Type: research

Apoptosis-inducing factor (Aif1) mediates anacardic acid-induced apoptosis in Saccharomyces cerevisiae
AbstractAnacardic acid is a medicinal phytochemical that inhibits proliferation of fungal as well as several types of cancer cells. It induces apoptotic cell death in various cell types, but very little is known about the mechanism involved in the process. Here, we used budding yeastSaccharomyces cerevisiae as a model to study the involvement of some key elements of apoptosis in the anacardic acid-induced cell death. Plasma membrane constriction, chromatin condensation, DNA degradation, and externalization of phosphatidylserine (PS) indicated that anacardic acid induces apoptotic cell death inS. cerevisiae. However, the ex...
Source: Apoptosis - December 22, 2016 Category: Molecular Biology Source Type: research

Adipocyte microenvironment promotes Bcl xl expression and confers chemoresistance in ovarian cancer cells
AbstractResistance to mitochondria-initiated apoptosis is a hallmark of chemoresistant cancer stem cells including CD44+/MyD88+ epithelial ovarian cancer (EOC) stem cells. This is controlled by members of the Bcl2 family of proteins, which function as rheostats of mitochondrial stability. We observed a differential expression profile of Bcl2 family members comparing the chemoresistant EOC stem cells and the chemosensitive CD44 −/MyD88− EOC cells. Chemoresistant EOC stem cells surprisingly express higher levels of the pro-apoptotic members Bak and Bax compared to the chemosensitive EOC cells. In addition, wherea...
Source: Apoptosis - December 22, 2016 Category: Molecular Biology Source Type: research

5-Flurouracil disrupts nuclear export and nuclear pore permeability in a calcium dependent manner
AbstractRegulation of nuclear transport is an essential component of apoptosis. As chemotherapy induced cell death progresses, nuclear transport and the nuclear pore complex (NPC) are slowly disrupted and dismantled. 5-Fluorouracil (5-FU) and the camptothecin derivatives irinotecan and topotecan, are linked to altered nuclear transport of specific proteins; however, their general effects on the NPC and transport during apoptosis have not been characterized. We demonstrate that 5-FU, but not topotecan, increases NPC permeability, and disrupts Ran-mediated nuclear transport before the disruption of the NPC. This increased pe...
Source: Apoptosis - December 19, 2016 Category: Molecular Biology Source Type: research

Natural products as modulator of autophagy with potential clinical prospects
AbstractNatural compounds derived from living organisms are well defined for their remarkable biological and pharmacological properties likely to be translated into clinical use. Therefore, delving into the mechanisms by which natural compounds protect against diverse diseases may be of great therapeutic benefits for medical practice. Autophagy, an intricate lysosome-dependent digestion process, with implications in a wide variety of pathophysiological settings, has attracted extensive attention over the past few decades. Hitherto, accumulating evidence has revealed that a large number of natural products are involved in a...
Source: Apoptosis - December 16, 2016 Category: Molecular Biology Source Type: research

Mycobacterium tuberculosis PE_PGRS18 enhances the intracellular survival of M. smegmatis via altering host macrophage cytokine profiling and attenuating the cell apoptosis
AbstractMycobacterium tuberculosis PE/PPE family proteins, named after the presence of conserved PE (Pro-Glu) and PPE (Pro-Pro-Glu) domains at N-terminal, are prevalent inM. tuberculosis genome. The function of most PE/PPE family proteins remains elusive. To characterize the function of PE_PGRS18, the encoding gene was heterologously expressed inM. smegmatis, a nonpathogenic mycobacterium. The recombinant PE_PGRS18 is cell wall associated.M. smegmatis PE_PGRS18 recombinant showed differential response to stresses and altered the production of host cytokines IL-6, IL-1 β, IL-12p40 and IL-10, as well as enhanced surviva...
Source: Apoptosis - December 15, 2016 Category: Molecular Biology Source Type: research

Two coffins and a funeral: early or late caspase activation determines two types of apoptosis induced by DNA damaging agents
AbstractCell cytoskeleton makes profound changes during apoptosis including the organization of an Apoptotic Microtubule Network (AMN). AMN forms a cortical structure which plays an important role in preserving plasma membrane integrity during apoptosis. Here, we examined the cytoskeleton rearrangements during apoptosis induced by camptothecin (CPT), a topoisomerase I inhibitor, in human H460 and porcine LLCPK-1 α cells. Using fixed and living cell imaging, we showed that CPT induced two dose- and cell cycle-dependent types of apoptosis characterized by different cytoskeleton reorganizations, time-dependent caspase a...
Source: Apoptosis - December 9, 2016 Category: Molecular Biology Source Type: research

Cardamonin represses proliferation, invasion, and causes apoptosis through the modulation of signal transducer and activator of transcription 3 pathway in prostate cancer
AbstractThe pleiotropic transcription factor, signal transducer and activator of transcription 3 (STAT3) is often aberrantly activated in a wide variety of cancers and plays a pivotal role in tumor initiation, promotion and progression. Targeting deregulated STAT3 activation by small molecule inhibitors is generally considered as an important therapeutic strategy. Hence, in the present study, we evaluated the potential of cardamonin (CD), a 2 ′,4′-dihydroxy-6′-methoxychalcone, to modulate STAT3 activation in prostate cancer (PC) cells and found that this chalcone can indeed exhibit significant anticancer ...
Source: Apoptosis - November 28, 2016 Category: Molecular Biology Source Type: research

The regulation of the mitochondrial apoptotic pathway by glucocorticoid receptor in collaboration with Bcl-2 family proteins in developing T cells
AbstractGlucocorticoids (GC) are important in the regulation of selection and apoptosis of CD4+CD8+ double-positive (DP) thymocytes. The pronounced GC-sensitivity of DP thymocytes, observed earlier, might be due to the combination of classical (genomic) and alternative (non-genomic) glucocorticoid receptor (GR) signaling events modifying activation or apoptotic pathways. In particular, the previously demonstrated mitochondrial translocation of activated GR in DP thymocytes offered a fascinating explanation for their pronounced GC-induced apoptosis sensitivity. However, the fine molecular details how the mitochondrial trans...
Source: Apoptosis - November 25, 2016 Category: Molecular Biology Source Type: research

A novel 4,6-disubstituted-1,2,4-triazolo-1,3,4-thiadiazole derivative inhibits tumor cell invasion and potentiates the apoptotic effect of TNF α by abrogating NF-κB activation cascade
In this study, several novel CBTT derivatives were synthesized and investigated for their possible role as anti-neoplastic agents. The anti-proliferative effect of various CBTT derivatives was analyzed against tumor cell lines by (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT assay. One of the potential CBTT derivative, 5-(3-(2,3-dichlorophenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-yl)flurobenzonitrile (DTTF) was found to be the most potent against cervical cancer SiHa cells and exhibited minimal effect against normal cells. Molecular docking analysis indicated that transcription factor NF- κ...
Source: Apoptosis - November 23, 2016 Category: Molecular Biology Source Type: research

Mille modis morimur : We die in a thousand ways
AbstractDying cells subjected to apoptotic programs are engulfed by neighboring cells or by professional phagocytes, without inflammation or immunological reactions in the tissue where apoptosis takes place. Apoptotic cells release danger-associated project signals to their neighbours, through different molecular patterns, stimulate antigen production and immune responses. Microenvironmental effects with several functional consequences indicate that cell death is a complex process and may take place in several ways. This idea is expressed by the title of the Special Issue and by the title of the guest editorial “Mill...
Source: Apoptosis - November 22, 2016 Category: Molecular Biology Source Type: research