Cardiac  Mitochondrial PTEN-L determines cell fate between apoptosis and survival during chronic alcohol consumption
AbstractChronic alcohol consumption induces myocardial damage and a type of non-ischemic cardiomyopathy termed alcoholic cardiomyopathy, where mitochondrial ultrastructural damages and suppressed fusion activity promote cardiomyocyte apoptosis. The aim of the present study is to determine the role of mitochondrial fission proteins and/or other proteins that localise on cardiac mitochondria for apoptosis upon ethanol consumption. In vivo and in vitro chronic alcohol exposure increased mitochondrial Drp1 levels but knockdown of the same did not confer cardioprotection in H9c2 cells. These cells displayed downregulated expres...
Source: Apoptosis - June 25, 2020 Category: Molecular Biology Source Type: research

The therapeutic strategy of drug re-positioning to induce autophagic cell death in brain malignancy
(Source: Apoptosis)
Source: Apoptosis - June 23, 2020 Category: Molecular Biology Source Type: research

The α7 and β2 nicotinic acetylcholine receptor subunits regulate apoptosis in the infant hippocampus, and in sudden infant death syndrome (SIDS)
AbstractApoptosis is increased in the hippocampus of infants who died of sudden infant death syndrome (SIDS), yet it is not known via which mechanism this has occurred. Following existing support for a role of the α7 and β2 nicotinic acetylcholine receptor (nAChR) subunits in apoptotic regulation, we aimed to determine whether these subunits are altered in the SIDS hippocampus and if they are correlated with cell death markers of active caspase-3 (Casp-3) and TUNEL. Further analyses were run according to t he presence of major SIDS risk factors related to hypoxia (bed-sharing and prone sleeping), infection ...
Source: Apoptosis - June 22, 2020 Category: Molecular Biology Source Type: research

The pro-apoptotic ARTS protein induces neutrophil apoptosis, efferocytosis, and macrophage reprogramming to promote resolution of inflammation
AbstractARTS (Sept4_i2) is a pro-apoptotic protein and a product of the Sept4 gene. ARTS acts upstream of mitochondria to initiate caspase activation. ARTS induces apoptosis by specifically binding XIAP and allowing de-repression of active caspases required for Mitochondrial Outer Membrane Permeabilzation (MOMP). Moreover, ARTS promotes apoptosis by inducing ubiquitin-mediated degradation of both major anti-apoptotic proteins XIAP and Bcl-2. In the resolution phase of inflammation, the infiltrating leukocytes, which execute the acute innate response, undergo apoptosis and are subsequently cleared by phagocytic macrophages ...
Source: Apoptosis - June 19, 2020 Category: Molecular Biology Source Type: research

Cytosolic DNA sensing through cGAS and STING is inactivated by gene mutations in pangolins
AbstractThe release of DNA into the cytoplasm upon damage to the nucleus or during viral infection triggers an interferon-mediated defense response, inflammation and cell death. In human cells cytoplasmic DNA is sensed by cyclic GMP-AMP Synthase (cGAS) and Absent In Melanoma 2 (AIM2). Here, we report the identification of a “natural knockout” model of cGAS. Comparative genomics of phylogenetically diverse mammalian species showed that cGAS and its interaction partner Stimulator of Interferon Genes (STING) have been inactivated by mutations in the Malayan pangolin whereas other mammals retained intact copies of ...
Source: Apoptosis - June 11, 2020 Category: Molecular Biology Source Type: research

Flow cytometric detection of hyper-polarized mitochondria in regulated and accidental cell death processes
AbstractShikonin induced necroptosis in Jurkat cells were  identified flow cytometrically by the up-regulation of RIP3 in live cells and that a proportion of these cells underwent other forms of regulated cell death (RCD) which included parthanatos (  40%), or cleaved PARP (>  15%) but less DNA Damage (
Source: Apoptosis - June 2, 2020 Category: Molecular Biology Source Type: research

Combination of a p53-activating CP-31398 and an MDM2 or a FAK inhibitor produces growth suppressive effects in mesothelioma with wild-type p53 genotype
We examined a growth suppressive activity of CP-31398 which was developed to restore the p53 functions irrespective of the genotype in mesothelioma with wild-type or mutatedp53. CP-31398 up-regulated p53 levels in cells with wild-typep53 genotype but induced cell growth suppression in a p53-independent manner. In contrasts, nutlin-3a, an MDM2 inhibitor, increased p53 and p21 levels in mesothelioma with the wild-typep53 genotype and produced growth suppressive effects. We investigated a combinatory effect of CP-31398 and nutlin-2a and found the combination produced synergistic growth inhibition in mesothelioma with the wild...
Source: Apoptosis - May 27, 2020 Category: Molecular Biology Source Type: research

Activation of β1 integrins and caveolin-1 by TF/FVIIa promotes IGF-1R signaling and cell survival
In conclusion, we present a plausible mechanism for the interplay between TF and IGF-1R involving FVIIa, β1-integrins, Src family proteins, and caveolin-1. Our results increase the knowledge of diseases associated with TF and IGF-1R overexpression in general but specifically of TF-mediated signaling with focus on cell survival. (Source: Apoptosis)
Source: Apoptosis - May 26, 2020 Category: Molecular Biology Source Type: research

Smac mimetics can provoke lytic cell death that is neither apoptotic nor necroptotic
AbstractSmac mimetics, or IAP antagonists, are a class of drugs currently being evaluated as anti-cancer therapeutics. These agents antagonize IAP proteins, including cIAP1/2 and XIAP, to induce cell death via apoptotic or, upon caspase-8 deficiency, necroptotic cell death pathways. Many cancer cells are unresponsive to Smac mimetic treatment as a single agent but can be sensitized to killing in the presence of the cytokine TNF α, provided either exogenously or via autocrine production. We found that high concentrations of a subset of Smac mimetics could provoke death in cells that did not produce TNFα, despite...
Source: Apoptosis - May 20, 2020 Category: Molecular Biology Source Type: research

Upregulation of microRNA-532 enhances cardiomyocyte apoptosis in the diabetic heart
In this study, we sought to determine whether diabetes induces dysregulation of miR-532 and if this is associated with accentuated apoptosis. RT-PCR analysis showed a significant increase in miR-532 expression in the right atrial appendage tissue of type 2 diabetic patients undergoing coronary artery bypass graft surgery. This was associated with marked downregulation of its anti-apoptotic target protein apoptosis repressor with caspase recruitment domain (ARC) and increased TUNEL positive cardiomyocytes. Further analysis showed a positive correlation between apoptosis and miR-532 levels. Time-course experiments in a mouse...
Source: Apoptosis - May 15, 2020 Category: Molecular Biology Source Type: research

Doxorubicin sensitizes cancer cells to Smac mimetic via synergistic activation of the CYLD/RIPK1/FADD/caspase-8-dependent apoptosis
AbstractSmac/Diablo is a pro-apoptotic protein via interaction with inhibitors of apoptosis proteins (IAPs) to relieve their inhibition of caspases. Smac mimetic compounds (also known as antagonists of IAPs) mimic the function of Smac/Diablo and sensitize cancer cells to TNF-induced apoptosis. However, the majority of cancer cells are resistant to Smac mimetic alone. Doxorubicin is a widely used chemotherapeutic drug and causes adverse effect of cardiotoxicity in many patients. Therefore, it is important to find strategies of combined chemotherapy to increase chemosensitivity and reduce the adverse effects. Here, we report...
Source: Apoptosis - May 15, 2020 Category: Molecular Biology Source Type: research

A potent protective effect of baicalein on liver injury by regulating mitochondria-related apoptosis
In this study, we aim to investigate the protective effects of baicalein on liver injury induced by oxidative stress. H2O2 and CCl4 were employed to establish liver injury models in vivo and in vitro, respectively. The protective effect of baicalein on oxidative stress –induced liver injury was evaluated by detecting the mitochondrial dynamics, the level of autophagy and apoptosis, the histopathology of liver, the indicators of liver function, and the level of oxidative stress in vitro and in vivo. March5 is the key regulator during liver injury induced by oxida tive stress. March5 can ubiquitinate Drp1 and promote D...
Source: Apoptosis - May 13, 2020 Category: Molecular Biology Source Type: research

Hemocompatible LAT1-inhibitor can induce apoptosis in cancer cells without affecting brain amino acid homeostasis
In this study, a previously reported LAT1-inhibitor (KMH-233) was studied for its hemocompatibility and toxicity towards human umbilical vein endothelial cells (HUVEC) and human aortic smooth muscle cells (AoSMCs). Furthermore, the cytotoxic effects against human breast adenocarcinoma cells (MCF-7) and its ability to affect mammalian (or mechanistic) target of rapamycin (mTOR) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF- κB) signaling were evaluated. Moreover, the effects of this inhibitor to modulate LAT1 function on the cell surface and the brain amino acid homeostasis were evaluated afte...
Source: Apoptosis - May 12, 2020 Category: Molecular Biology Source Type: research

Gedunin isolated from the mangrove plant Xylocarpus granatum exerts its anti-proliferative activity in ovarian cancer cells through G2/M-phase arrest and oxidative stress-mediated intrinsic apoptosis
AbstractGedunin is a natural tetranorterpenoid secondary metabolite found in plants of the Meliaceae family, which has been reported for its antiparasitic, antifungal and anticancer activities. Here, we describe the molecular mechanisms underlying the in vitro anti proliferative activity of gedunin (isolated from the mangrove plantXylocarpus granatum) in human ovarian cancer cells. We observed that gedunin triggered severe ROS generation leading to DNA damage and cell cycle arrest in G2/M phase thus inhibiting cell proliferation. ROS upregulation also led to mitochondrial stress and membrane depolarization, which eventuall...
Source: Apoptosis - May 12, 2020 Category: Molecular Biology Source Type: research

Citarinostat and Momelotinib co-target HDAC6 and JAK2/STAT3 in lymphoid malignant cell lines: a potential new therapeutic combination
AbstractHistone deacetylase (HDAC) inhibitors represent an encouraging class of antitumor drugs. HDAC inhibitors induce a series of molecular and biological responses and minimal toxicity to normal cells. Citarinostat (Acy-241) is a second generation, orally administered, HDAC6-selective inhibitor. Momelotinib (CYT387) is an orally administered inhibitor of Janus kinase/signal transducer of transcription-3 (JAK/STAT3) signaling. Momelotinib showed efficacy in patients with myelofibrosis. We hypothesized that both HDAC and JAK/STAT pathways were important in lymphoproliferative disorders, and that inhibiting JAK/STAT3 and H...
Source: Apoptosis - May 10, 2020 Category: Molecular Biology Source Type: research

The function of RNase L and its degradation mechanism in cardiac acute ischemic injury
In this study, we tested the hypothesis that RNase L may be involved in the pathological process of cardiac ischemic injury. RNase L-overexpressing and RNase L knockdown H9c2 cell lines were subjected to the oxygen and glucose deprivation (OGD) model, and RNase L knockout mice were subjected to acute myocardial infarction surgical procedures to investigate the function of RNase L in ischemic heart injury. OGD induced abnormal aggregation of double-stranded RNA in H9c2 cells, activated RNase L within 6  h of OGD initiation, and mediated apoptosis via the c-Jun N-terminal kinase pathway. In addition, RNase L knockout mi...
Source: Apoptosis - May 7, 2020 Category: Molecular Biology Source Type: research

Baicalein attenuates caspase-independent cells death via inhibiting PARP-1 activation and AIF nuclear translocation in cerebral ischemia/reperfusion rats
AbstractIt is reported that baicalein can activate PI3K/AKT pathway, inhibit caspase activation and reduce cerebral infarct volume in middle cerebral artery occlusion (MCAO) rats. However, a caspase-independent mechanism initiated by poly (ADP-ribose) polymerase-1 (PARP-1) activation has been reported to make more contribution to cells death after ischemic stroke. In the present study, we established a cerebral ischemia/reperfusion (I/R) rat model through middle cerebral artery occlusion following reperfusion to investigate the mechanisms of ischemic tissue recovery following baicalein treatment. The data showed that baica...
Source: Apoptosis - April 26, 2020 Category: Molecular Biology Source Type: research

BCL-2 family deregulation in colorectal cancer: potential for BH3 mimetics in therapy
AbstractApoptosis is a form of programmed cell death that is essential for tissue homeostasis. De-regulation of the balance between proliferation and apoptosis contributes to tumor initiation. Particularly in the colon where apoptosis is a crucial process in intestinal turnover, inhibition of apoptosis facilitates transformation and tumor progression. The BCL-2 family of proteins are key regulators of apoptosis and have been implicated in colorectal cancer (CRC) initiation, progression and resistance to therapy. In this review we outline the current knowledge on the BCL-2 family-regulated intrinsic apoptosis pathway and me...
Source: Apoptosis - April 24, 2020 Category: Molecular Biology Source Type: research

Soluble receptor for advanced glycation end-products promotes angiogenesis through activation of STAT3 in myocardial ischemia/reperfusion injury
AbstractSoluble receptor for advanced glycation end-products (sRAGE), which exerts cardioprotective effect through inhibiting cardiomyocyte apoptosis and autophagy during ischemia/reperfusion (I/R) injury, is also known to enhance angiogenesis in post-ischemic reperfusion injury-critical limb ischemia (PIRI-CLI) mice. However, whether sRAGE protects the heart from myocardial I/R injury via promoting angiogenesis remains unclear. Myocardial model of I/R injury was conducted by left anterior descending (LAD) ligation for 30 min and reperfusion for 2 weeks in C57BL/6 mice. And I/R injury in cardiac microvascular endothelial c...
Source: Apoptosis - April 23, 2020 Category: Molecular Biology Source Type: research

miR-21 protects neonatal rats from hypoxic-ischemic brain damage by targeting CCL3
AbstractHypoxic-ischemic brain damage (HIBD) represents one of the leading causes of neonatal mortality and permanent neurological disability worldwide. Compelling studies have identified implication of microRNAs (miRNAs) in HIBD. However, the molecular mechanism of miR-21 underlying the disease pathogenesis is unknown. The present study aims to explore the role of miR-21 in neonatal rats with HIBD. HIBD rat models were developed by carotid artery ligation and hypoxia treatment, and in vitro cell models were induced by oxygen –glucose deprivation. Through RT-qPCR and western blot analysis, high expression of CCL3 and...
Source: Apoptosis - April 17, 2020 Category: Molecular Biology Source Type: research

Glucocorticoid-induced autophagy and apoptosis in bone
AbstractGlucocorticoids are widely prescribed to treat various allergic and autoimmune diseases; however, long-term use results in glucocorticoid-induced osteoporosis, characterized by consistent changes in bone remodeling with decreased bone formation as well as increased bone resorption. Not only bone mass but also bone quality decrease, resulting in an increased incidence of fractures. The primary role of autophagy is to clear up damaged cellular components such as long-lived proteins and organelles, thus participating in the conservation of different cells. Apoptosis is the physiological death of cells, and plays a cru...
Source: Apoptosis - March 9, 2020 Category: Molecular Biology Source Type: research

Programmed death, cells on the last train to glory
(Source: Apoptosis)
Source: Apoptosis - March 6, 2020 Category: Molecular Biology Source Type: research

Abdominal paracentesis drainage attenuates severe acute pancreatitis by enhancing cell apoptosis via PI3K/AKT signaling pathway
AbstractOur previous studies have shown that abdominal paracentesis drainage (APD) is a safe and effective strategy for patients with severe acute pancreatitis (SAP). However, the underlying mechanisms behind APD treatment remain poorly understood. Given that apoptosis is a critical pathological response of SAP, we here aim to investigate the effect of APD on cell apoptosis in pancreatic tissues during SAP and to explore its potential molecular mechanism. SAP was induced by 5% sodium-taurocholate retrograde while APD group was inserted a drainage tube into the right lower abdomen of rats immediately after SAP induction. Hi...
Source: Apoptosis - February 24, 2020 Category: Molecular Biology Source Type: research

BRAFi induced demethylation of miR-152-5p regulates phenotype switching by targeting TXNIP in cutaneous melanoma
AbstractTreatment of advanced BRAFV600-mutant melanoma using BRAF inhibitors (BRAFi) eventually leads to drug resistance and selects for highly metastatic tumor cells. We compared the most differentially dysregulated miRNA expression profiles of vemurafenib-resistant and highly-metastatic melanoma cell lines obtained from GEO DataSets. We discovered miR-152-5p was a potential regulator mediating melanoma drug resistance and metastasis. Functionally, knockdown of miR-152-5p significantly compromised the metastatic ability of BRAFi-resistant melanoma cells and overexpression of miR-152-5p promoted the formation of slow-cycli...
Source: Apoptosis - February 12, 2020 Category: Molecular Biology Source Type: research

Exploitation of a novel phenothiazine derivative for its anti-cancer activities in malignant glioblastoma
This study adopts a drug repurposing approach by investigating the anti-cancer activity of a derivative of the antipsychotic drug phenothiazine (DS00329) in malignant U251 and U87 glioblastoma cells. Results from MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and clonogenic assays showed that DS00329 inhibited short-term glioblastoma cell viability and long-term survival while sparing non-cancerous cells. Western  blot analysis with an antibody to γH2AX showed that DS00329 induced DNA damage and flow cytometry and western blotting confirmed that it triggered a G1 cell cycle arrest which corre...
Source: Apoptosis - February 7, 2020 Category: Molecular Biology Source Type: research

Potent antitumor activity of oncolytic adenovirus expressing C/EBP β against hepatocellular carcinoma
(Source: Apoptosis)
Source: Apoptosis - February 4, 2020 Category: Molecular Biology Source Type: research

Synergism of 4HPR and SAHA increases anti-tumor actions in glioblastoma cells
AbstractGlioblastoma is the most malignant and prevalent brain tumor in adults. It can grow and spread quickly causing harm to the brain health. One of the major challenges in treatment of glioblastoma is drug resistance. Use of synergistic combination of two drugs with different anti-tumor effects is nowadays highly considered in the development of effective therapeutic strategies for many malignancies. In the present study, we showed synergistic therapeutic efficacies of two chemical compounds,N-(4-hydroxyphenyl) retinamide (4HPR) and suberoylanilide hydroxamic acid (SAHA), for significant reduction in cell viability of ...
Source: Apoptosis - January 30, 2020 Category: Molecular Biology Source Type: research

Loss of BIM in T cells results in BCL-2 family BH3-member compensation but incomplete cell death sensitivity normalization
This study further highlights the importance of BIM in cell death maintenance in T cells and provides new insight into the dynamism underlying BH3-only regulation of T cell homeostasis versus induced cell death and suggests that CD4+ and CD8+ T cells compensate differently in response to loss ofBim. (Source: Apoptosis)
Source: Apoptosis - January 27, 2020 Category: Molecular Biology Source Type: research

Lactate accelerates vascular calcification through NR4A1-regulated mitochondrial fission and BNIP3-related mitophagy
This study suggests that the NR4A1/DNA-PKcs/p53 pathway is involved in the mechanism by which lactate accelerates vascular calcification, partly through excessive Drp-mediated mitochondrial fission and BNIP3-related mitophagy deficiency. (Source: Apoptosis)
Source: Apoptosis - January 27, 2020 Category: Molecular Biology Source Type: research

DDX3 modulates cisplatin resistance in OSCC through ALKBH5-mediated m 6 A-demethylation of FOXM1 and NANOG
In this study we found genetic (shRNA) or pharmacological (ketorolac salt) inhibition of DDX3 reduced CSC population by suppressing the expression of FOXM1 and NANOG. We also found that m6A demethylase ALKBH5 is directly regulated by DDX3 which leads to decreased m6A methylation in FOXM1 and NANOG nascent transcript that contribute to chemoresistance. Here, we found DDX3 expression was upregulated in both cisplatin-resistant OSCC lines and chemoresistant tumors when compared with their respective sensitive counterparts. In a patient-derived cell xenograft model of chemoresistant OSCC, ketorolac salt restores cisplatin-medi...
Source: Apoptosis - January 22, 2020 Category: Molecular Biology Source Type: research

microRNA-499a promotes the progression and chemoresistance of cervical cancer cells by targeting SOX6
AbstractEmerging evidence has indicated that microRNAs are involved in multiple processes of cancer development. Previous studies have demonstrated that microRNA-499a (miR-499a) plays both oncogenic and tumor suppressive roles in several types of malignancies, and genetic variants in miR-499a are associated with the risk of cervical cancer. However, the biological roles of miR-499a in cervical cancer have not been investigated. Quantitative real-time PCR was used to assess miR-499a expression in cervical cancer cells. Mimics or inhibitor of miR-499a was transfected into cervical cancer cells to upregulate or downregulate m...
Source: Apoptosis - January 13, 2020 Category: Molecular Biology Source Type: research

Necroptosis and its role in infectious diseases
AbstractNecroptosis is a noncaspase-dependent and precisely regulated mechanism of cell death. Necroptosis is mainly initiated by members of the tumor necrosis factor receptor (TNFR) and Toll-like receptor (TLR) families, interferon, intracellular RNA and DNA sensors and other mediators. Subsequently, the protein kinase RIPK1 (receptor-interacting protein kinase 1) and RIPK3 interact with the receptor protein, which transduces death signals and further recruits and phosphorylates MLKL (mixed lineage kinase domain-like protein). MLKL serves as the initiator of cell death and eventually induces necroptosis. It was found that...
Source: Apoptosis - January 6, 2020 Category: Molecular Biology Source Type: research

PDGFR β-targeted TRAIL specifically induces apoptosis of activated hepatic stellate cells and ameliorates liver fibrosis
In this study, we found that platelet-derived growth factor receptor β (PDGFRβ) was co-expressed with DR5 in aHSCs. And the ZPDGFR β affibody with high affinity for PDGFR β could bind aHSCs and, thus, accumulate in the fibrotic liver. ZPDGFR β was fused to hTRAIL to produce the fusion protein Z-hTRAIL. Compared to hTRAIL, Z-hTRAIL showed greater in vitro cell binding and apoptosis-induction in aHSCs. In addition, Z-hTRAIL induced apoptosis of aHSCs but spared other normal liver cells. In vivo, Z-hTRAIL accumulated preferentially in fibrotic livers and exerted greater effects than hTRAIL in inducing...
Source: Apoptosis - December 31, 2019 Category: Molecular Biology Source Type: research

Artemisinin and dihydroartemisinin promote β-cell apoptosis induced by palmitate via enhancing ER stress
In this study, the rat pancreatic β-cell line INS-1 and mouse pancreatic β-cell line MIN6 were cultured with palmitate (PA) (0.1 mM) to induce cell apoptosis in the presence or absence of ART or DHA. Cell apoptosis was investigated by using flow cytometry, and the expression of ER stress markers, including CHOP, GRP78 and PDI, was detected by Western blotting and/or qRT-PCR. The results showed that ART and DHA significantly increased the apoptosis of β-cells induced by PA and exacerbated the ER stress caused by PA. An inhibitor of ER stress, 4-phenylbutyric acid (4-PBA), sig nificantly ameliorated cell ...
Source: Apoptosis - December 31, 2019 Category: Molecular Biology Source Type: research

Lysophosphatidic acid promotes survival of T lymphoma cells by altering apoptosis and glucose metabolism
AbstractLysophosphatidic acid (LPA) is a bioactive lipid, which plays an indispensable role in various physiological and pathological processes. Moreover, an elevated level of LPA has been observed in malignancies of different origins and implicated in their progression via modulation of proliferation, apoptosis, invasion and metastasis. Interestingly, few recent reports suggest a pivotal role of LPA-modulated metabolism in oncogenesis of ovarian cancer. However, little is understood regarding the role of LPA in the development and progression of T cell malignancies, which are considered as one of the most challenging neop...
Source: Apoptosis - December 22, 2019 Category: Molecular Biology Source Type: research

Liposomal encapsulation of silver nanoparticles (AgNP) improved nanoparticle uptake and induced redox imbalance to activate caspase-dependent apoptosis
AbstractMacrophages play a crucial role in several diseases ’ development and progression, such as in cancer and arthritis through ROS generation and inflammation. This makes macrophages a therapeutic target in these diseases. While silver nanoparticles (AgNP) have been widely used as an antibacterial and investigated as anticancer, its potential against m acrophages may be limited due to its inherent oxidative mechanism. Here we encapsulated AgNP in a dipalmitoyl-phosphatidyl choline (DPPC) liposome (forming Lipo-AgNP) to suppress AgNP-induced ROS and enhance its cytotoxicity against THP1-differentiated macrophages ...
Source: Apoptosis - December 19, 2019 Category: Molecular Biology Source Type: research

MicroRNA-214 targets COX-2 to antagonize indoxyl sulfate (IS)-induced endothelial cell apoptosis
In conclusion, this study demonstrated an important role of miR-214 in protecting against endothelial cell damage induced by IS possibly by direct downregulation of COX-2/PGE2 axis. (Source: Apoptosis)
Source: Apoptosis - December 8, 2019 Category: Molecular Biology Source Type: research

Correction to: M1 macrophage dependent-p53 regulates the intracellular survival of mycobacteria
The original version of this article unfortunately contains an error in the acknowledgement section. The text “Brain Korea 21 PLUS Project for Medical Science, Chungnam National University” was omitted by mistake. The correct and complete acknowledgment is given below: Acknowledgments This work was supported by the research fund of Chungnam National University and the Brain Korea 21 PLUS Project for Med ical Science, Chungnam National University. The funders had no role in study design, data collection and analysis decision to publish, or preparation of the manuscript. (Source: Apoptosis)
Source: Apoptosis - November 26, 2019 Category: Molecular Biology Source Type: research

Effect of miR-27b-5p on apoptosis of human vascular endothelial cells induced by simulated microgravity
AbstractWeightlessness-induced cardiovascular dysfunction can lead to physiological and pathological consequences. It has been shown that spaceflight or simulated microgravity can alter expression profiles of some microRNAs (miRNAs). Here, we attempt to identify the role of miRNAs in human umbilical vein endothelial cells (HUVECs) apoptosis under simulated microgravity. RNA-sequencing and quantitative real-time PCR (qRT-PCR) assays were used to identify differentially expressed miRNAs in HUVECs under simulated microgravity. Then we obtained the target genes of these miRNAs through target analysis software. Moreover, GO and...
Source: Apoptosis - November 24, 2019 Category: Molecular Biology Source Type: research

Klotho-mediated changes in the expression of Atg13 alter formation of ULK1 complex and thus initiation of ER- and Golgi-stress response mediated autophagy
In this study, we have performed a detailed step-by-step analysis of autophagy flux-related genes ’ expression and endoplasmic reticulum and Golgi stress related pathways in order to determine the exact mechanistic event when autophagy is inhibited in klotho-deficient cells on account of apoptosis initiation. We provide evidence thatklotho-silencing in LPS-treated cells results in differential course of ER- and Golgi-mediated stress response. Further, we show that inklotho-deficient cells formation of ULK1 complex is inhibited and thus autophagy initiation is blocked on the account of apoptosis activation, while in t...
Source: Apoptosis - November 14, 2019 Category: Molecular Biology Source Type: research

M1 macrophage dependent-p53 regulates the intracellular survival of mycobacteria
In this study, we found that the p53-deficient macrophages failed to controlMycobacterium tuberculosis (Mtb), manifested as a lower apoptotic cell death rate and enhanced intracellular survival. The expression levels of p53 during Mtb infection were stronger in M1 macrophages than in M2 macrophages. The TLR2/JNK signaling pathway plays an essential role in the modulation of M1 macrophage polarization upon Mtb infection. It facilitates p53-mediated apoptosis through the production of reactive oxygen species, nitric oxide and inflammatory cytokines in Mtb-infected M1 macrophages. In addition, nutlin-3 effectively abrogated t...
Source: Apoptosis - November 4, 2019 Category: Molecular Biology Source Type: research

Influenza A virus-induced apoptosis and virus propagation
AbstractInfluenza A viruses (IAVs) are respiratory pathogens that cause severe morbidity and mortality worldwide. They affect cellular processes such as proliferation, protein synthesis, autophagy, and apoptosis. Although apoptosis is considered an innate cellular response to invading infectious pathogens, IAVs have evolved to encode viral proteins that modulate host cellular apoptosis in ways that support efficient viral replication and propagation. An understanding of the modulation of host responses is essential to the development of novel therapeutics for the treatment of IAV infections. In this review, we discuss the ...
Source: Apoptosis - October 29, 2019 Category: Molecular Biology Source Type: research

Inhibitors of HSP90 in melanoma
AbstractHSP90 (heat shock protein 90) is an ATP-dependent molecular chaperone involved in a proper folding and maturation of hundreds of proteins. HSP90 is abundantly expressed in cancer, including melanoma. HSP90 client proteins are the key oncoproteins of several signaling pathways controlling melanoma development, progression and response to therapy. A number of natural and synthetic compounds of different chemical structures and binding sites within HSP90 have been identified as selective HSP90 inhibitors. The majority of HSP90-targeting agents affect N-terminal ATPase activity of HSP90. In contrast to N-terminal inhib...
Source: Apoptosis - October 27, 2019 Category: Molecular Biology Source Type: research

Accumulation of tissue factor in endothelial cells promotes cellular apoptosis through over-activation of Src1 and involves β1-integrin signalling
In this study, the involvement of Src1 in the induction of TF-mediated cell apoptosis, and the mechanisms of Src1 activation were investigated. Human coronary artery endothelial cell (HCAEC) were transfected with plasmids to express the wild-type TF (TFWt-tGFP), or a mutant (Ser253  → Ala) which is incapable of being released from cells (TFAla253-tGFP). The cells were then activated with PAR2-agonist peptide (SLIGKV-NH) and the phosphorylation of Src and Rac, and also the kinase activity of Src were assessed. Transfected cells were also pre-incubated with pp60c Src inhibitor, FAK inhibitor-14, or a block...
Source: Apoptosis - October 24, 2019 Category: Molecular Biology Source Type: research

Integrin-EGFR interaction regulates anoikis resistance in colon cancer cells
AbstractAnoikis resistance is an essential property of cancer cells that allow the extra-cellular matrix-detached cells to survive in a suspended state in body fluid in order to metastasize and invade to distant organs. It is known that integrins play an important role in anoikis resistance, but detailed mechanisms are not well understood. Here we report that highly metastatic colon cancer cells showed a higher degree of anoikis resistance than the normal intestinal epithelial cells. These anoikis-resistant cancer cells express high-levels of integrin- α2, β1, and activated EGFR in the anchorage-independent stat...
Source: Apoptosis - October 21, 2019 Category: Molecular Biology Source Type: research

Two-factor specification of apoptosis: TGF- β signaling acts cooperatively with ecdysone signaling to induce cell- and stage-specific apoptosis of larval neurons during metamorphosis in Drosophila melanogaster
AbstractDevelopmentally regulated programmed cell death (PCD) is one of the key cellular events for precise controlling of neuronal population during postembryonic development of the central nervous system. Previously we have shown that a group of corazonin-producing peptidergic neurons (vCrz) undergo apoptosis in response to ecdysone signaling via ecdysone receptor (EcR)-B isoforms and Ultraspiracle during early phase of metamorphosis. Further utilizing genetic, transgenic, and mosaic analyses, we have found that TGF- β signaling mediated by a glia-produced ligand, Myoglianin, type-I receptor Baboon (particularly Bab...
Source: Apoptosis - October 21, 2019 Category: Molecular Biology Source Type: research

PP2Ac upregulates PI3K-Akt signaling and induces hepatocyte apoptosis in liver donor after brain death
AbstractMultiple research groups have demonstrated that the outcome of patients receiving liver grafts from brain death donors (DBD) is poorer when compared with patients receiving grafts from living donors. This might be due to an increased hepatocyte apoptosis induced after brain death (BD). In this work, we found that the activity of PP2A-Akt pathway is significantly increased in clinical donor ex vivo hepatocytes after BD by iTRAQ protein quantification analysis. The same results were confirmed in animal models. A time-dependent promotion of apoptosis was also found in DBD rabbit liver, as demonstrated by the increased...
Source: Apoptosis - October 10, 2019 Category: Molecular Biology Source Type: research

Loss of HMBOX1 promotes LPS-induced apoptosis and inhibits LPS-induced autophagy of vascular endothelial cells in mouse
In conclusion, HMBOX1 participated in the functional maintenance of mouse aortic endothelial cells, the aortic endothelial cells of HMBOX1 KO mouse showed increased apopt osis and decreased autophagy with LPS treatment. (Source: Apoptosis)
Source: Apoptosis - October 2, 2019 Category: Molecular Biology Source Type: research

Liver-specific Bid silencing inhibits APAP-induced cell death in mice
In conclusion, the liver-specific silencing of Bid expression did not protect APAP-exposed mice from microcirculatory dysfunction, but markedly protected the liver from necrotic cell death and in consequence from sterile inflammation. The study contributes to the understanding of the molecular mechanism of the APAP-induced pathogenic pathway by strengthening the importance of Bid and Bid silencing associated effects. (Source: Apoptosis)
Source: Apoptosis - September 30, 2019 Category: Molecular Biology Source Type: research

Correction to: Defining the role of cytoskeletal components in the formation of apoptopodia and apoptotic bodies during apoptosis
The original version of the article unfortunately contained a typo in the fourth author name. The author name was incorrectly listed as Rochelle Tixeria. The correct name should be Rochelle Tixeira. The original article has been corrected. (Source: Apoptosis)
Source: Apoptosis - September 22, 2019 Category: Molecular Biology Source Type: research