The antineoplastic agent α-bisabolol promotes cell death by inducing pores in mitochondria and lysosomes
Abstract The sesquiterpene α-bisabolol (α-BSB) has been shown to be an effective cytotoxic agent for a variety of human cancer cells in culture and animal models. However, much of its intracellular action remains elusive. We evaluated the cytotoxic action of α-BSB against CML-T1, Jurkat and HeLa cell lines, as preclinical models for myeloid, lymphoid and epithelial neoplasias. The approach included single cell analysis (flow cytometry, immunocytology) combined with cytotoxicity and proliferation assays to characterize organelle damage, autophagy, cytostatic effect, and apoptosis. The study focuse...
Source: Apoptosis - June 8, 2016 Category: Molecular Biology Source Type: research

SIRT1 activation by pterostilbene attenuates the skeletal muscle oxidative stress injury and mitochondrial dysfunction induced by ischemia reperfusion injury
In conclusion, PTE has protective properties against IR injury of the skeletal muscles. The mechanism of this protective effect depends on the activation of the SIRT1-FOXO1/p53 signaling pathway and the decrease of the apoptotic ratio in skeletal muscle cells. (Source: Apoptosis)
Source: Apoptosis - June 8, 2016 Category: Molecular Biology Source Type: research

Csk regulates angiotensin II-induced podocyte apoptosis
This study evaluates the role of Csk in Ang II-induced podocyte apoptosis. In vivo, Wistar rats were randomly subjected to a normal saline or Ang II infusion. In vitro, we exposed differentiated mouse podocytes to Ang II. Ang II increased Csk expression and induced podocyte apoptosis, stimulated Csk translocation and binding to Caveolin-1, and stimulated decreased Fyn pY416, increased Fyn pY529, and nephrin dephosphorylation. Csk knockdown prevented Ang II-induced podocyte apoptosis, reduced Fyn kinase inactivation, and increased the interaction between nephrin and the activated form of Fyn, accompanied by a reduced intera...
Source: Apoptosis - May 25, 2016 Category: Molecular Biology Source Type: research

Detergent sclerosants at sub-lytic concentrations induce endothelial cell apoptosis through a caspase dependent pathway
Abstract To investigate the apoptotic effects of detergent sclerosants sodium tetradecylsulphate (STS) and polidocanol (POL) on endothelial cells at sub-lytic concentrations. Human umbilical vein endothelial cells (HUVECs) were isolated and labelled with antibodies to assess for apoptosis and examined with confocal microscopy and flow cytometry. Isolated HUVECs viability was assessed using propidium iodide staining. Early apoptosis was determined by increased phosphatidylserine exposure by lactadherin binding. Caspase 3, 8, 9 and Bax activation as well as inhibitory assays with Pan Caspase (Z-VAD-FMK) and Bax (BI-...
Source: Apoptosis - May 25, 2016 Category: Molecular Biology Source Type: research

Scolopendin 2 leads to cellular stress response in Candida albicans
In conclusion, treatment of C. albicans with scolopendin 2 induced the apoptotic response at sublethal doses, which in turn led to mitochondrial dysfunction, metacaspase activation, and cell death. The cationic antimicrobial peptide scolopendin 2 from the centipede is a potential antifungal peptide, triggering the apoptotic response. (Source: Apoptosis)
Source: Apoptosis - May 20, 2016 Category: Molecular Biology Source Type: research

Current situation and future usage of anticancer drug databases
Abstract Cancer is a deadly disease with increasing incidence and mortality rates and affects the life quality of millions of people per year. The past 15 years have witnessed the rapid development of targeted therapy for cancer treatment, with numerous anticancer drugs, drug targets and related gene mutations been identified. The demand for better anticancer drugs and the advances in database technologies have propelled the development of databases related to anticancer drugs. These databases provide systematic collections of integrative information either directly on anticancer drugs or on a specific type o...
Source: Apoptosis - May 18, 2016 Category: Molecular Biology Source Type: research

Melatonin reduces PERK-eIF2α-ATF4-mediated endoplasmic reticulum stress during myocardial ischemia–reperfusion injury: role of RISK and SAFE pathways interaction
In this study, we performed in vivo and in vitro experiment to investigate the ameliorative effect of melatonin on ER stress with a focus on RISK and SAFE pathways interaction. Male C57Bl/6 mice received melatonin (300 μg/25 g/day, 3 days before MI/R surgery; 300 μg/25 g, 25 min before the onset of ischemia) pre-treatment with or without the administration of LY294002 (a PI3K/Akt inhibitor), U0126 (an ERK1/2 inhibitor) or AG490 (a STAT3 pathway inhibitor). H9c2 cells were pre-treated with melatonin (100 μM, 8 h) in the presence or absence of LY294002, U0126 or AG490. Compare...
Source: Apoptosis - May 11, 2016 Category: Molecular Biology Source Type: research

The fungicide Mancozeb induces metacaspase-dependent apoptotic cell death in Saccharomyces cerevisiae BY4741
Abstract Mancozeb (MZ), a mixture of ethylene-bis-dithiocarbamate manganese and zinc salts, is one of the most widely used fungicides in agriculture. Toxicologic studies in mammals and mammalian cells indicate that this fungicide can cause neurological and cytological disorders, putatively associated with pro-oxidant and apoptotic effects. Yeast adaptation to sub-inhibitory concentrations of MZ has been correlated with oxidative response, proteins degradation, and energy metabolism, and its main effect on yeast has been attributed to its high reactivity with thiol groups in proteins. Herein, we show that acute...
Source: Apoptosis - May 9, 2016 Category: Molecular Biology Source Type: research

Advanced oxidative protein products induced human keratinocyte apoptosis through the NOX–MAPK pathway
Abstract Impaired wound healing is a major diabetes-related complication. Keratinocytes play an important role in wound healing. Multiple factors have been proposed that can induce dysfunction in keratinocytes. The focus of present research is at a more specific molecular level. We investigated the role of advanced oxidative protein products (AOPPs) in inducing human immortalized keratinocyte (HaCaT) cell apoptosis and the cellular mechanism underlying the proapoptotic effect of AOPPs. HaCaT cells were treated with increasing concentrations of AOPP–human serum albumin or for increasing time durations. The ce...
Source: Apoptosis - May 7, 2016 Category: Molecular Biology Source Type: research

Cytotoxic activity of the novel heterocyclic compound G-11 is primarily mediated through intrinsic apoptotic pathway
This study comprehensively details the possible mechanisms of action of a novel heterocyclic compound which could find its potential use as an anticancer agent. (Source: Apoptosis)
Source: Apoptosis - May 6, 2016 Category: Molecular Biology Source Type: research

Mycobacterium tuberculosis PE13 (Rv1195) manipulates the host cell fate via p38-ERK-NF-κB axis and apoptosis
Abstract PE/PPE family proteins are mycobacteria unique molecules, named after their N-terminal conserved PE (Pro-Glu) and PPE (Pro-Pro-Glu) domains. Mycobacterium tuberculosis (Mtb) PE family gene encoded cell surface proteins are previously reported to be involved in virulence and interaction with host. To explore the role of a novel PE member (PE13, Rv1195), M. smegmatis was used as surrogate host. The study showed that Rv1195 was a cell wall associated protein. Rv1195 can enhance the survival of recombinants under stress conditions such as H2O2, SDS, low pH. This is largely due to the upregulated transcription...
Source: Apoptosis - May 4, 2016 Category: Molecular Biology Source Type: research

Caspases and their role in inflammation and ischemic neuronal death. Focus on caspase-12
Abstract Caspases are cysteine proteases, which play important roles in different processes including, apoptosis and inflammation. Caspase-12, expressed in mouse and human, is classified as an inflammatory caspase. However, in humans caspase-12 gene has acquired different mutations that result in the expression of different variants. Caspase-12 is generally recognized as a negative regulator of the inflammatory response induced by infections, because it inhibits the activation of caspase-1 in inflammasome complexes, the production of the pro-inflammatory cytokines IL-1β and IL-18 and the overall response to s...
Source: Apoptosis - May 3, 2016 Category: Molecular Biology Source Type: research

Clinical and pathological significance of N-Myc downstream-regulated gene 2 (NDRG2) in diverse human cancers
Abstract Human N-Myc downstream-regulated gene 2 (NDRG2), located at chromosome 14q11.2, has been reported to be down-regulated and associated with the progression and prognosis of diverse cancers. Collectively, previous studies suggest that NDRG2 functions as a candidate tumor-suppressor gene; thus, up-regulation of NDRG2 protein might act as a promising therapeutic strategy for malignant tumors. The aim of this review was to comprehensively present the clinical and pathological significance of NDRG2 in human cancers. (Source: Apoptosis)
Source: Apoptosis - April 25, 2016 Category: Molecular Biology Source Type: research

Apoptosis and autophagy induced by pyropheophorbide-α methyl ester-mediated photodynamic therapy in human osteosarcoma MG-63 cells
Abstract Pyropheophorbide-α methyl ester (MPPa) was a second-generation photosensitizer with many potential applications. Here, we explored the impact of MPPa-mediated photodynamic therapy (MPPa-PDT) on the apoptosis and autophagy of human osteosarcoma (MG-63) cells as well as the relationships between apoptosis and autophagy of the cells, and investigated the related molecular mechanisms. We found that MPPa-PDT demonstrated the ability to inhibit MG-63 cell viability in an MPPa concentration- and light dose-dependent manner, and to induce apoptosis via the mitochondrial apoptosis pathway. Additionally,...
Source: Apoptosis - April 23, 2016 Category: Molecular Biology Source Type: research

Erratum to: Polymorphisms of extrinsic death receptor apoptotic genes (FAS −670 G>A, FASL −844 T>C) in coronary artery disease
(Source: Apoptosis)
Source: Apoptosis - April 20, 2016 Category: Molecular Biology Source Type: research

Sodium orthovanadate suppresses palmitate-induced cardiomyocyte apoptosis by regulation of the JAK2/STAT3 signaling pathway
Abstract Elevated circulatory free fatty acids (FFAs) especially saturated FFAs, such as palmitate (PA), are detrimental to the heart. However, mechanisms responsible for this phenomenon remain unknown. Here, the role of JAK2/STAT3 in PA-induced cytotoxicity was investigated in cardiomyocytes. We demonstrate that PA suppressed the JAK2/STAT3 pathway by dephosphorylation of JAK2 (Y1007/1008) and STAT3 (Y705), and thus blocked the translocation of STAT3 into the nucleus. Conversely, phosphorylation of S727, another phosphorylated site of STAT3, was increased in response to PA treatment. Pretreatment of JNK inhi...
Source: Apoptosis - April 13, 2016 Category: Molecular Biology Source Type: research

Combinatorial treatment with anacardic acid followed by TRAIL augments induction of apoptosis in TRAIL resistant cancer cells by the regulation of p53, MAPK and NFκβ pathways
Abstract TRAIL, an apoptosis inducing cytokine currently in phase II clinical trial, was investigated for its capability to induce apoptosis in six different human tumor cell lines out of which three cell lines showed resistance to TRAIL induced apoptosis. To investigate whether Anacardic acid (A1) an active component of Anacardium occidentale can sensitize the resistant cell lines to TRAIL induced apoptosis, we treated the resistant cells with suboptimal concentration of A1 and showed that it is a potent enhancer of TRAIL induced apoptosis which up-regulates the expression of both DR4 and DR5 receptors, which ha...
Source: Apoptosis - April 13, 2016 Category: Molecular Biology Source Type: research

Suppression of c-Myc induces apoptosis via an AMPK/mTOR-dependent pathway by 4- O -methyl-ascochlorin in leukemia cells
Abstract 4-O-Methyl-ascochlorin (MAC) is a methylated derivative of the prenyl-phenol antibiotic ascochlorin, which was isolated from an incomplete fungus, Ascochyta viciae. Although the effects of MAC on apoptosis have been reported, the underlying mechanisms remain unknown. Here, we show that MAC promoted apoptotic cell death and downregulated c-Myc expression in K562 human leukemia cells. The effect of MAC on apoptosis was similar to that of 10058-F4 (a c-Myc inhibitor) or c-Myc siRNA, suggesting that the downregulation of c-Myc expression plays a role in the apoptotic effect of MAC. Further investigation show...
Source: Apoptosis - April 13, 2016 Category: Molecular Biology Source Type: research

Polymorphisms of extrinsic death receptor apoptotic genes (FAS −670 G>A, FASL −844 T>C) in coronary artery disease
Abstract Apoptosis plays an important role in atherogenesis and rupture of vulnerable plaques in coronary artery disease. FAS and FAS ligand (FASL) induce apoptosis when FAS binds to FAS-L. However sFas blocks apoptosis by binding to FAS and FASL or sFasL. The present study is sought to examine the role of extrinsic apoptotic genes (FAS, FASL) polymorphism and serum levels of FAS, FASL in the pathogenesis and susceptibility to CAD in south Indian population. The study included 300 CAD patients and 300 healthy controls. Lipid profiles, sFas, sFasL were estimated by commercially available kits. FAS −670 G>...
Source: Apoptosis - April 13, 2016 Category: Molecular Biology Source Type: research

Erratum to: Injection of Aβ1-40 into hippocampus induced cognitive lesion associated with neuronal apoptosis and multiple gene expressions in the tree shrew
(Source: Apoptosis)
Source: Apoptosis - April 7, 2016 Category: Molecular Biology Source Type: research

Actin depolymerization mediated loss of SNTA1 phosphorylation and Rac1 activity has implications on ROS production, cell migration and apoptosis
In this study, we present the interplay between f-actin, SNTA1 and Rac1. We analyzed the effect of actin depolymerization on SNTA1 tyrosine phosphorylation and Rac1 activity using actin depolymerizing drugs, cytochalasin D and latrunculin A. Our results indicate a marked decrease in the tyrosine phosphorylation of SNTA1 upon actin depolymerization. Results suggest that actin depolymerization mediated loss of SNTA1 phosphorylation leads to loss of interaction between SNTA1 and Rac1, with a concomitant loss of Rac1 activation. The loss of SNTA1tyrosine phosphorylation and Rac1 activity by actin depolymerization results in in...
Source: Apoptosis - April 5, 2016 Category: Molecular Biology Source Type: research

MicroRNA-30 inhibits antiapoptotic factor Mcl-1 in mouse and human hematopoietic cells after radiation exposure
Abstract We previously reported that microRNA-30 (miR-30) expression was initiated by radiation-induced proinflammatory factor IL-1β and NFkB activation in mouse and human hematopoietic cells. However, the downstream effectors of miR-30 and its specific role in radiation-induced cell death are not well understood. In the present study, we evaluated effects of radiation on miR-30 expression and activation of intrinsic apoptotic pathway Bcl-2 family factors in in vivo mouse and in vitro human hematopoietic cells. CD2F1 mice and human CD34+ cells were exposed to different doses of gamma-radiation. In additi...
Source: Apoptosis - March 31, 2016 Category: Molecular Biology Source Type: research

Erratum to: Suppression of c-Myc induces apoptosis via an AMPK/mTOR-dependent pathway by 4- O -methyl-ascochlorin in leukemia cells
(Source: Apoptosis)
Source: Apoptosis - March 31, 2016 Category: Molecular Biology Source Type: research

Eupatilin induces Sestrin2-dependent autophagy to prevent oxidative stress
Abstract Eupatilin (5,7-dihydroxy-3,4,6-trimethoxyflavone) has many pharmacological activities including anti-inflammation, anti-oxidant and anti-cancer effects. Autophagy is the basic cellular machinery involving the digestion of damaged cellular components. In the present study, we investigated the protection effects of eupatilin against arachidonic acid (AA) and iron-induced oxidative stress in HepG2 cells and tried to elucidate the molecular mechanisms responsible. Eupatilin increased cell viability against AA + iron in a concentration-dependent manner and prevented mitochondrial dysfunction and reac...
Source: Apoptosis - March 25, 2016 Category: Molecular Biology Source Type: research

Unravelling the relationship between macroautophagy and mitochondrial ROS in cancer therapy
Abstract Macroautophagy (Autophagy), an evolutionarily conserved cellular self-digesting process implicated in various physiological and pathological processes, is activated by different stimuli including oxidative stress. Reactive oxygen species (ROS) are involved in autophagy modulation through multiple signaling pathways and transcription regulators. Accumulating data support both a positive and negative role of ROS-modulated autophagy in cancer. As a tumor suppressive mechanism, autophagy induces autophagic cell death and maintains genome stability. Conversely, autophagy may promote cancer development by limit...
Source: Apoptosis - March 23, 2016 Category: Molecular Biology Source Type: research

Deconvoluting the relationships between autophagy and metastasis for potential cancer therapy
Abstract Autophagy is a highly conserved lysosome-dependent degradation process that may digest some long-lived proteins and damaged organelles. As an essential homeostasis maintaining system in normal cells, autophagy plays a key role in several pathological settings, especially cancer. Metastasis, known as a crucial hallmark of cancer progression, is the primary cause of cancer lethality. The role of autophagy in metastasis is quite complex as supportive evidence has indicated both pro-metastatic and anti-metastatic functions of autophagy. Autophagy can inhibit metastasis by restricting necrosis and mediating au...
Source: Apoptosis - March 22, 2016 Category: Molecular Biology Source Type: research

Bakuchiol attenuates myocardial ischemia reperfusion injury by maintaining mitochondrial function: the role of silent information regulator 1
This study was designed to investigate the protective effects of BAK treatment in the setting of myocardial IRI and to elucidate the potential mechanism of those effects. Prior to induction of IR, isolated rat hearts or cardiomyocytes were exposed to BAK in either the absence or presence of the SIRT1 inhibitors Sirtinol and SIRT1 siRNA. BAK exerted cardioprotective effects, as evidenced by the improvements noted in cardiac function following ischemia, attenuated myocardial apoptosis, and changes in several biochemical parameters (including increases in the level of the anti-apoptotic protein Bcl2, decreases in the level of...
Source: Apoptosis - March 21, 2016 Category: Molecular Biology Source Type: research

Varying butyric acid amounts induce different stress- and cell death-related signals in nerve growth factor-treated PC12 cells: implications in neuropathic pain absence during periodontal disease progression
In this study, we exposed NGF-treated PC12 cells to varying BA concentrations [0 (control), 0.5, 1.0, 5.0 mM] and determined selected stress-related (H2O2, glutathione reductase, calcium (Ca2+), plasma membrane Ca2+ ATPase (PMCA), and GADD153/CHOPS) and cell death-associated (extrinsic: FasL, TNF-α, TWEAK, and TRAIL; intrinsic: cytochrome C (CytC), NF-kB, CASP8, CASP9, CASP10, and CASP3) signals. Similarly, we confirmed cell death execution by chromatin condensation. Our results showed that low (0.5 mM) and high (1.0 and 5.0 mM) BA levels differ in stress and cell death signaling. Moreover, at periodon...
Source: Apoptosis - March 19, 2016 Category: Molecular Biology Source Type: research

Berberine activates Nrf2 nuclear translocation and inhibits apoptosis induced by high glucose in renal tubular epithelial cells through a phosphatidylinositol 3-kinase/Akt-dependent mechanism
In this study, the underlying mechanisms involved in the protective effects of BBR on high glucose-induced apoptosis were explored using cultured renal tubular epithelial cells (NRK-52E cells) and human kidney proximal tubular cell line (HK-2 cells). We identified the pivotal role of phosphatidylinositol 3-kinase (PI3K)/Akt in BBR cellular defense mechanisms and revealed the novel effect of BBR on nuclear factor (erythroid-derived 2)-related factor-2 (Nrf2) and heme oxygenase (HO)-1 in NRK-52E and HK-2 cells. BBR attenuated reactive oxygen species production, antioxidant defense (GSH and SOD) and oxidant-sensitive proteins...
Source: Apoptosis - March 15, 2016 Category: Molecular Biology Source Type: research

Erratum to: DAPK plays an important role in panobinostat-induced autophagy and commits cells to apoptosis under autophagy deficient conditions
(Source: Apoptosis)
Source: Apoptosis - March 10, 2016 Category: Molecular Biology Source Type: research

Injection of Aβ1-40 into hippocampus induced cognitive lesion associated with neuronal apoptosis and multiple gene expressions in the tree shrew
This study utilized twelve adult male tree shrews (TS), which were randomly divided into PBS and amyloidbetapeptide1-40 (Aβ1-40) groups. AD model was established via an intracerebroventricular (icv) injection of Aβ1-40 after being incubated for 4 days at 37 °C. Behavioral, pathophysiological and molecular changes were evaluated by hippocampal-dependent tasks, magnetic resonance imaging (MRI), silver staining, hematoxylin–eosin (HE) staining, TUNEL assay and gene sequencing, respectively. At 4 weeks post-injection, as compared with the PBS group, in Aβ1-40 injected animals: cognitive ...
Source: Apoptosis - February 20, 2016 Category: Molecular Biology Source Type: research

PAR-1 mediated apoptosis of breast cancer cells by V. cholerae hemagglutinin protease
In this study we report that HAP induced activation and over expression of PAR-1 in breast cancer cells (EAC). Immunoprecipitation studies have shown that HAP specifically binds with PAR-1. HAP mediated activation of PAR-1 caused nuclear translocation of p50–p65 and the phosphorylation of p38 which triggered the activation of NFκB and MAP kinase signaling pathways. These signaling pathways enhanced the cellular ROS level in malignant cells that induced the intrinsic pathway of cell apoptosis. PAR-1 mediated apoptosis by HAP of malignant breast cells without effecting normal healthy cells in the same enviro...
Source: Apoptosis - February 20, 2016 Category: Molecular Biology Source Type: research

Sec6/8 regulates Bcl-2 and Mcl-1, but not Bcl-xl, in malignant peripheral nerve sheath tumor cells
This study demonstrates that combination of doxorubicin and sorafenib induces apoptosis in MPNST cells through downregulation of B cell lymphoma protein 2 (Bcl-2), Bcl-2-related protein long form of Bcl-x (Bcl-xl), and myeloid cell leukemia 1 (Mcl-1). Moreover, both Sec6 and Sec8 levels decreased after treatment with doxorubicin and sorafenib and were found to be associated with Bcl-2 and Mcl-1 expressions, but not Bcl-xl. Although Sec8 was found to be involved in the regulation of both Bcl-2 and Mcl-1 at the mRNA level, Sec6 regulated Bcl-2 at the mRNA level and the binding affinity of F-box and WD repeat domain containin...
Source: Apoptosis - February 18, 2016 Category: Molecular Biology Source Type: research

Gadd45b prevents autophagy and apoptosis against rat cerebral neuron oxygen-glucose deprivation/reperfusion injury
In conclusion, our data suggested that Gadd45b inhibited autophagy and apoptosis under OGD/R. Gadd45b may be a common regulatory protein to control autophagy and apoptosis. (Source: Apoptosis)
Source: Apoptosis - February 16, 2016 Category: Molecular Biology Source Type: research

Eosinophil resistance to glucocorticoid-induced apoptosis is mediated by the transcription factor NFIL3
Abstract The mainstay of asthma therapy, glucocorticoids (GCs) exert their therapeutic effects through the inhibition of inflammatory signaling and induction of eosinophil apoptosis. However, laboratory and clinical observations of GC-resistant asthma suggest that GCs’ effects on eosinophil viability may depend on the state of eosinophil activation. In the present study we demonstrate that eosinophils stimulated with IL-5 show impaired pro-apoptotic response to GCs. We sought to determine the contribution of GC-mediated transactivating (TA) and transrepressing (TR) pathways in modulation of activated eosinop...
Source: Apoptosis - February 15, 2016 Category: Molecular Biology Source Type: research

Anticancer potential of pyrrole (1, 2, a) pyrazine 1, 4, dione, hexahydro 3-(2-methyl propyl) (PPDHMP) extracted from a new marine bacterium, Staphylococcus sp. strain MB30
Abstract Marine bacterium, strain MB30 isolated from the deep sea sediment of Bay of Bengal, India, exhibited antimicrobial activity against human pathogenic bacteria. Based on the 16S rRNA sequence homology and subsequent phylogenetic tree analysis, the strain MB30 was identified as Staphylococcus sp. The bioactive metabolite produced by the strain MB30 was purified through silica gel column chromatography and preparative HPLC. Purified metabolite was further characterized by FT-IR, LC–MS and NMR analyses. On the basis of spectroscopic data, the metabolite was identified as pyrrole (1, 2, a) pyrazine 1, 4, ...
Source: Apoptosis - February 6, 2016 Category: Molecular Biology Source Type: research

Mycobacterium avium MAV2052 protein induces apoptosis in murine macrophage cells through Toll-like receptor 4
In this study, using multidimensional fractionation, we identified MAV2052 protein, which induced macrophage apoptosis in M. avium culture filtrates. The recombinant MAV2052 induced macrophage apoptosis in a caspase-dependent manner. The loss of mitochondrial transmembrane potential (ΔΨm), mitochondrial translocation of Bax, and release of cytochrome c from mitochondria were observed in macrophages treated with MAV2052. Further, reactive oxygen species (ROS) production was required for the apoptosis induced by MAV2052. In addition, ROS and mitogen-activated protein kinases were involved in MAV2052-mediated TNF-&a...
Source: Apoptosis - February 3, 2016 Category: Molecular Biology Source Type: research

Profilin potentiates chemotherapeutic agents mediated cell death via suppression of NF-κB and upregulation of p53
Abstract The molecular mechanism by which Profilin acts as a tumor suppressor is still unclear. Several chemotherapeutic agents, used till date either have unfavorable side effects or acquired resistance in tumor cells. Our findings show that Profilin enhances cell death mediated by several chemotherapeutic-agents. The activation of NF-κB and its dependent genes, mediated by paclitaxel and vinblastine, was completely inhibited in Profilin overexpressing cells. This inhibition was due to the Profilin mediated attenuation of IκBα degradation, thereby preventing p65 nuclear translocation and low NF-...
Source: Apoptosis - February 3, 2016 Category: Molecular Biology Source Type: research

GSIV serine/threonine kinase can induce apoptotic cell death via p53 and pro-apoptotic gene Bax upregulation in fish cells
In this study, we demonstrated that the Giant seaperch iridovirus (GSIV) genome encoded a serine/threonine kinase (ST kinase) protein, and induced apoptotic cell death via a p53-mediated Bax upregulation approach and a downregulation of Bcl-2 in fish cells. The ST kinase expression profile was identified through Western blot analyses, which indicated that expression started at day 1 h post-infection (PI), increased up to day 3, and then decreased by day 5 PI. This profile indicated the role of ST kinase expression during the early and middle phases of viral replication. We then cloned the ST kinase gene and tested its...
Source: Apoptosis - January 30, 2016 Category: Molecular Biology Source Type: research

Erratum to: Phosphocreatine protects against LPS-induced human umbilical vein endothelial cell apoptosis by regulating mitochondrial oxidative phosphorylation
(Source: Apoptosis)
Source: Apoptosis - January 29, 2016 Category: Molecular Biology Source Type: research

Knockdown of α-synuclein in cerebral cortex improves neural behavior associated with apoptotic inhibition and neurotrophin expression in spinal cord transected rats
Abstract Spinal cord injury (SCI) often causes severe functional impairment with poor recovery. The treatment, however, is far from satisfaction, and the mechanisms remain unclear. By using proteomics and western blot, we found spinal cord transection (SCT) resulted in a significant down-regulation of α-synuclein (SNCA) in the motor cortex of SCT rats at 3 days post-operation. In order to detect the role of SNCA, we used SNCA-ORF/shRNA lentivirus to upregulate or knockdown SNCA expression. In vivo, SNCA-shRNA lentivirus injection into the cerebral cortex motor area not only inhibited SNCA expression, bu...
Source: Apoptosis - January 28, 2016 Category: Molecular Biology Source Type: research

Inhibition of heme oxygenase-1 enhances the chemosensitivity of laryngeal squamous cell cancer Hep-2 cells to cisplatin
Abstract It has been previously reported that cisplatin is a well-known anticancer drug being used against a wide range of malignancies including head and neck, ovarian and non-small cell lung carcinoma, and demonstrated its anticancer activity by reacting with DNA or changing cell structure, immune response, reactive oxygen species level (ROS). In this research we proved that cisplatin induced cell injuries and heme oxygenase-1 (HO-1) expression in laryngeal squamous cell cancer Hep-2 cells through ROS generation. The induction of HO-1 clearly protected Hep-2 cells from cisplatin-induced cell death and ROS reacti...
Source: Apoptosis - January 22, 2016 Category: Molecular Biology Source Type: research

Caspase-12 is involved in stretch-induced apoptosis mediated endoplasmic reticulum stress
This study seeks to determine if caspase-12 is involved in stretch-induced apoptosis mediated endoplasmic reticulum stress in myoblast and its underlying mechanism. Apoptosis was assessed by Hochest staining, DAPI staining and annexin V binding and PI staining. ER chaperones, such as GRP78, CHOP and caspase-12, were determined by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Furthermore, caspase-12 inhibitor was used to value the mechanism of the caspase-12 pathway. Apoptosis of myoblast, which is subjected to cyclic stretch, was observed in a time-dependent manner. We found that GRP78 mRNA and...
Source: Apoptosis - January 22, 2016 Category: Molecular Biology Source Type: research

Necroptosis: a potential, promising target and switch in acute pancreatitis
This article reviewed the progress of necroptosis in AP to provide a reference for deeply understanding the pathogenic mechanisms of AP and identifying new therapeutic targets. (Source: Apoptosis)
Source: Apoptosis - January 14, 2016 Category: Molecular Biology Source Type: research

Enhanced autophagy reveals vulnerability of P-gp mediated epirubicin resistance in triple negative breast cancer cells
Abstract Epirubicin (EPI) is widely used for triple negative breast cancer (TNBC), but a substantial number of patients develop EPI resistance that is associated with poor outcome. The underlying mechanism for EPI resistance remains poorly understood. We have developed and characterized an EPI-resistant (EPI-R) cell line from parental MDA-MB-231 cells. These EPI-R cells reached stable growth in the medium containing 8 μg/ml of EPI. They overexpressed P-glycoprotein (P-gp) and contained numerous autophagic vacuoles. The suppression of P-gp overexpression and/or autophagy restored the sensitivity of these EP...
Source: Apoptosis - January 14, 2016 Category: Molecular Biology Source Type: research

Human islet cells are killed by BID-independent mechanisms in response to FAS ligand
Abstract Cell death via FAS/CD95 can occur either by activation of caspases alone (extrinsic) or by activation of mitochondrial death signalling (intrinsic) depending on the cell type. The BH3-only protein BID is activated in the BCL-2-regulated or mitochondrial apoptosis pathway and acts as a switch between the extrinsic and intrinsic cell death pathways. We have previously demonstrated that islets from BID-deficient mice are protected from FAS ligand-mediated apoptosis in vitro. However, it is not yet known if BID plays a similar role in human beta cell death. We therefore aimed to test the role of BID in human ...
Source: Apoptosis - January 12, 2016 Category: Molecular Biology Source Type: research

Membrane-bound heat shock proteins facilitate the uptake of dying cells and cross-presentation of cellular antigen
Abstract Heat shock proteins (HSPs) were originally identified as stress-responsive proteins and serve as molecular chaperones in different intracellular compartments. Translocation of HSPs to the cell surface and release of HSPs into the extracellular space have been observed during the apoptotic process and in response to a variety of cellular stress. Here, we report that UV irradiation and cisplatin treatment rapidly induce the expression of membrane-bound Hsp60, Hsp70, and Hsp90 upstream the phosphatidylserine exposure. Membrane-bound Hsp60, Hsp70 and Hsp90 could promote the release of IL-6 and IL-1β...
Source: Apoptosis - January 1, 2016 Category: Molecular Biology Source Type: research

Advanced oxidation protein products induce chondrocyte apoptosis via receptor for advanced glycation end products-mediated, redox-dependent intrinsic apoptosis pathway
Abstract Pro-inflammatory cytokine-induced chondrocyte apoptosis is a primary cause of cartilage destruction in the progression of rheumatoid arthritis (RA). Advanced oxidation protein products (AOPPs), a novel pro-inflammatory mediator, have been confirmed to accumulate in patients with RA. However, the effect of AOPPs accumulation on chondrocyte apoptosis and the associated cellular mechanisms remains unclear. The present study demonstrated that the plasma formation of AOPPs was enhanced in RA rats compared with normal. Then, chondrocyte were treated with AOPPs-modified rat serum albumin (AOPPs-RSA) in vitro. E...
Source: Apoptosis - January 1, 2016 Category: Molecular Biology Source Type: research

Bcl-2 silencing attenuates hypoxia-induced apoptosis resistance in pulmonary microvascular endothelial cells
This study therefore reveals critical insight into potential therapeutic targets for treating PAH. (Source: Apoptosis)
Source: Apoptosis - January 1, 2016 Category: Molecular Biology Source Type: research

Role of CSL-dependent and independent Notch signaling pathways in cell apoptosis
Abstract Apoptosis is a normally biological phenomenon in various organisms, involving complexly molecular mechanisms with a series of signaling processes. Notch signaling is found evolutionarily conserved in many species, playing a critical role in embryonic development, normal tissue homeostasis, angiogenesis and immunoregulation. The focus of this review is on currently novel advances about roles of CSL-dependent and independent Notch signaling pathways in cell apoptosis. The CSL can bind Notch intracellular domain (NIC) to act as a switch in mediating transcriptional activation or inactivation of th...
Source: Apoptosis - January 1, 2016 Category: Molecular Biology Source Type: research