The influenza A virus PB1-F2 protein targets the inner mitochondrial membrane via a predicted basic amphipathic helix that disrupts mitochondrial function.
'The 11th influenza A virus gene product is an 87-amino-acid protein provisionally named PB1-F2 (because it is encoded by an open reading frame overlapping the PB1 open reading frame). A significant fraction of PB1-F2 localizes to the inner mitochondrial membrane in influenza A virus-infected cells. PB1-F2 appears to enhance virus-induced ... More
High-resolution mapping reveals topologically distinct cellular pools of phosphatidylserine.
AuthorsFairn GD, Schieber NL, Ariotti N, Murphy S, Kuerschner L, Webb RI, Grinstein S, Parton RG,
JournalJ Cell Biol
PubMed ID21788369
'Phosphatidylserine (PS) plays a central role in cell signaling and in the biosynthesis of other lipids. To date, however, the subcellular distribution and transmembrane topology of this crucial phospholipid remain ill-defined. We transfected cells with a GFP-tagged C2 domain of lactadherin to detect by light and electron microscopy PS exposed ... More
Nuclear relocation of the nephrin and CD2AP-binding protein dendrin promotes apoptosis of podocytes.
AuthorsAsanuma K, Campbell KN, Kim K, Faul C, Mundel P
JournalProc Natl Acad Sci U S A
PubMed ID17537921
'Kidney podocytes and their slit diaphragms (SDs) form the final barrier to urinary protein loss. There is mounting evidence that SD proteins also participate in intracellular signaling pathways. The SD protein nephrin serves as a component of a signaling complex that directly links podocyte junctional integrity to actin cytoskeletal dynamics. ... More
Transcriptional up-regulation of ULK1 by ATF4 contributes to cancer cell survival.
AuthorsPike LR, Singleton DC, Buffa F, Abramczyk O, Phadwal K, Li JL, Simon AK, Murray JT, Harris AL
JournalBiochem J
PubMed ID23078367
'Hypoxia in the microenvironment of many solid tumours is an important determinant of malignant progression. The ISR (integrated stress response) protects cells from the ER (endoplasmic reticulum) stress caused by severe hypoxia. Likewise, autophagy is a mechanism by which cancer cells can evade hypoxic cell death. In the present paper ... More
Phosphorylation of inositol 1,4,5-trisphosphate receptors by protein kinase B/Akt inhibits Ca2+ release and apoptosis.
AuthorsSzado T, Vanderheyden V, Parys JB, De Smedt H, Rietdorf K, Kotelevets L, Chastre E, Khan F, Landegren U, Söderberg O, Bootman MD, Roderick HL,
JournalProc Natl Acad Sci U S A
PubMed ID18250332
'Imbalance of signals that control cell survival and death results in pathologies, including cancer and neurodegeneration. Two pathways that are integral to setting the balance between cell survival and cell death are controlled by lipid-activated protein kinase B (PKB)/Akt and Ca(2+). PKB elicits its effects through the phosphorylation and inactivation ... More
Simultaneous detection of apoptosis and mitochondrial superoxide production in live cells by flow cytometry and confocal microscopy.
AuthorsMukhopadhyay P, Rajesh M, Haskó G, Hawkins BJ, Madesh M, Pacher P
JournalNat Protoc
PubMed ID17853886
'Annexin V and Sytox Green are widely used markers to evaluate apoptosis in various cell types using flow cytometry and fluorescent microscopy. Recently, a novel fluoroprobe MitoSOX Red was introduced for selective detection of superoxide in the mitochondria of live cells and was validated for confocal microscopy and flow cytometry. ... More
Notch signaling expands a pre-malignant pool of T-cell acute lymphoblastic leukemia clones without affecting leukemia-propagating cell frequency.
AuthorsBlackburn JS, Liu S, Raiser DM, Martinez SA, Feng H, Meeker ND, Gentry J, Neuberg D, Look AT, Ramaswamy S, Bernards A, Trede NS, Langenau DM
JournalLeukemia
PubMed ID22538478
'NOTCH1 pathway activation contributes to the pathogenesis of over 60% of T-cell acute lymphoblastic leukemia (T-ALL). While Notch is thought to exert the majority of its effects through transcriptional activation of Myc, it also likely has independent roles in T-ALL malignancy. Here, we utilized a zebrafish transgenic model of T-ALL, ... More
In vitro culture medium influences the vaccine efficacy of Mycobacterium bovis BCG.
AuthorsVenkataswamy MM, Goldberg MF, Baena A, Chan J, Jacobs WR, Porcelli SA
JournalVaccine
PubMed ID22189700
'The varied rates of protection induced by Mycobacterium bovis BCG vaccine against tuberculosis has been attributed to many factors such as genetic variability among BCG strains, rapid clearance of BCG in some populations, and different levels of previous exposure of vaccinated populations to environmental mycobacteria. However, the methods and conditions ... More
Polo-like kinase inhibitor Ro5203280 has potent antitumor activity in nasopharyngeal carcinoma.
'Nasopharyngeal carcinoma is a cancer with its highest prevalence among the southern Chinese and is rare elsewhere in the world. The main treatment modalities include chemotherapy and radiotherapy. However, tumor chemoresistance often limits the efficacy of nasopharyngeal carcinoma treatment and reduces survival rates. Thus, identifying new selective chemotherapeutic drugs for ... More
A targeted RNAi screen of the breast cancer genome identifies KIF14 and TLN1 as genes that modulate docetaxel chemosensitivity in triple-negative breast cancer.
'To identify biomarkers within the breast cancer genome that may predict chemosensitivity in breast cancer. We conducted an RNA interference (RNAi) screen within the breast cancer genome for genes whose loss-of-function enhanced docetaxel chemosensitivity in an estrogen receptor-negative, progesterone receptor-negative, and Her2-negative (ER-, PR-, and Her2-, respectively) breast cancer cell ... More
Natural antibodies of newborns recognize oxidative stress-related malondialdehyde acetaldehyde adducts on apoptotic cells and atherosclerotic plaques.
AuthorsWang C, Turunen SP, Kummu O, Veneskoski M, Lehtimäki J, Nissinen AE, Hörkkö S,
Journal
PubMed ID23900424
'Malondialdehyde acetaldehyde (MAA) adducts are generated under oxidative stress and shown to be highly immunogenic. Our aim was to investigate the recognition of MAA adducts by human natural antibodies in newborns before or at the time of full-term pregnancy. Plasma samples of pre-term (n = 11) and full-term (n = ... More
Modulation of inositol polyphosphate levels regulates neuronal differentiation.
AuthorsLoss O, Wu CT, Riccio A, Saiardi A,
Journal
PubMed ID23864704
'The binding of neurotrophins to tropomyosin receptor kinase receptors initiates several signaling pathways, including the activation of phospholipase C-?, which promotes the release of diacylglycerol and inositol 1,4,5-trisphosphate (IP(3)). In addition to recycling back to inositol, IP(3) serves as a precursor for the synthesis of higher phosphorylated inositols, such as ... More
A method for measurement of drug sensitivity of myeloma cells co-cultured with bone marrow stromal cells.
AuthorsMisund K, Baranowska KA, Holien T, Rampa C, Klein DC, Børset M, Waage A, Sundan A,
JournalJ Biomol Screen
PubMed ID23446700
'The tumor microenvironment can profoundly affect tumor cell survival as well as alter antitumor drug activity. However, conventional anticancer drug screening typically is performed in the absence of stromal cells. Here, we analyzed survival of myeloma cells co-cultured with bone marrow stromal cells (BMSC) using an automated fluorescence microscope platform, ... More
Mitochondrially mediated integrin aIIbß3 protein inactivation limits thrombus growth.
When platelets are strongly stimulated, a procoagulant platelet subpopulation is formed that is characterized by phosphatidylserine (PS) exposure and epitope modulation of integrin aIIbß3 or a loss of binding of activation-dependent antibodies. Mitochondrial permeability transition pore (mPTP) formation, which is essential for the formation of procoagulant platelets, is impaired in ... More
Vitellogenin recognizes cell damage through membrane binding and shields living cells from reactive oxygen species.
AuthorsHavukainen H, Münch D, Baumann A, Zhong S, Halskau Ø, Krogsgaard M, Amdam GV,
Journal
PubMed ID23897804
Large lipid transfer proteins are involved in lipid transportation and diverse other molecular processes. These serum proteins include vitellogenins, which are egg yolk precursors and pathogen pattern recognition receptors, and apolipoprotein B, which is an anti-inflammatory cholesterol carrier. In the honey bee, vitellogenin acts as an antioxidant, and elevated vitellogenin ... More
Mitochondrial Staining Allows Robust Elimination of Apoptotic and Damaged Cells during Cell Sorting.
AuthorsBarteneva NS, Ponomarev ED, Tsytsykova A, Armant M, Vorobjev IA,
Journal
PubMed ID24394470
High-speed fluorescence-activated cell sorting is relevant for a plethora of applications, such as PCR-based techniques, microarrays, cloning, and propagation of selected cell populations. We suggest a simple cell-sorting technique to eliminate early and late apoptotic and necrotic cells, with good signal-to-noise ratio and a high-purity yield. The mitochondrial potential dye, ... More
Comparison of the C2A domain of synaptotagmin-I and annexin-V as probes for detecting cell death.
AuthorsAlam IS, Neves AA, Witney TH, Boren J, Brindle KM,
JournalBioconjug Chem
PubMed ID20402461
The induction of apoptosis is frequently accompanied by the exposure of phosphatidylserine (PS) on the cell surface, which has been detected using radionuclide and fluorescently labeled derivatives of the PS-binding protein, Annexin V. The fluorescently labeled protein has been used extensively in vitro as a diagnostic reagent for detecting cell ... More
Mechanisms of hepatocellular toxicity associated with dronedarone--a comparison to amiodarone.
AuthorsFelser A, Blum K, Lindinger PW, Bouitbir J, Krähenbühl S,
JournalToxicol Sci
PubMed ID23135547
Dronedarone is a new antiarrhythmic drug with an amiodarone-like benzofuran structure. Shortly after its introduction, dronedarone became implicated in causing severe liver injury. Amiodarone is a well-known mitochondrial toxicant. The aim of our study was to investigate mechanisms of hepatotoxicity of dronedarone in vitro and to compare them with amiodarone. ... More
Multiparametric analysis of cells with different mitochondrial membrane potential during apoptosis by polychromatic flow cytometry.
AuthorsTroiano L, Ferraresi R, Lugli E, Nemes E, Roat E, Nasi M, Pinti M, Cossarizza A,
JournalNat Protoc
PubMed ID18007607
The analysis of changes in mitochondrial membrane potential (MMP) that can occur during apoptosis provides precious information on the mechanisms and pathways of cell death. For many years, the metachromatic fluorochrome JC-1 (5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide) was used for this purpose. Thanks to new dyes and to the technical improvements recently adopted ... More
Confocal restricted-height imaging of suspension cells (CRISC) in a PDMS microdevice during apoptosis.
AuthorsMuñoz-Pinedo C, Green DR, van den Berg A
JournalLab Chip
PubMed ID15915255
We have monitored and imaged cell death induced in human leukemic U937 cells over time using three-color confocal imaging. Three different apoptotic inducers, anti-Fas, TNF-alpha and Etoposide were used. Individual cascaded events such as loss of mitochondrial transmembrane potential, exposure of phosphatidyl-serine, membrane blebbing and permeabilization of the cell membrane ... More
ATF4 orchestrates a program of BH3-only protein expression in severe hypoxia.
AuthorsPike LR, Phadwal K, Simon AK, Harris AL
JournalMol Biol Rep
PubMed ID23090478
Intratumoral hypoxia is associated with poor prognosis, regardless of the mode of therapy. Cancer cells survive this condition through activating several adaptive signaling pathways, including the integrated stress response (ISR) and autophagy. Activating transcription factor 4 (ATF4) is the major transcriptional mediator of the ISR, which we have shown to ... More
Quantum dots based probes conjugated to annexin V for photostable apoptosis detection and imaging.
AuthorsLe Gac S, Vermes I, van den Berg A
JournalNano Lett
PubMed ID16967992
Quantum dots (Qdots) are nanoparticles exhibiting fluorescent properties that can be used for cell staining. We present here the development of quantum dots conjugated to Annexin V for specific targeting of apoptotic cells, for both apoptosis detection and staining of apoptotic "living" cells. For that purpose, Qdots Streptavidin Conjugates are ... More
Cytochrome c is released in a single step during apoptosis.
AuthorsGoldstein JC, Muñoz-Pinedo C, Ricci JE, Adams SR, Kelekar A, Schuler M, Tsien RY, Green DR
JournalCell Death Differ
PubMed ID15933725
Release of cytochrome c from mitochondria is a central event in apoptotic signaling. In this study, we utilized a cytochrome c fusion that binds fluorescent biarsenical ligands (cytochrome c-4CYS (cyt. c-4CYS)) as well as cytochrome c-green fluorescent protein (cyt. c-GFP) to measure its release from mitochondria in different cell types ... More
Targeting malignant B cells with an immunotoxin against ROR1.
AuthorsBaskar S, Wiestner A, Wilson WH, Pastan I, Rader C
JournalMAbs
PubMed ID22531447
The selective cell surface expression of receptor tyrosine kinase-like orphan receptor 1 (ROR1) in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) has made ROR1 a novel and promising target for therapeutic monoclonal antibodies (mAbs). Four mouse mAbs generated by hybridoma technology exhibited specific binding to human ROR1. Epitope ... More
Dual role of platelet protein kinase C in thrombus formation: stimulation of pro-aggregatory and suppression of procoagulant activity in platelets.
AuthorsStrehl A, Munnix IC, Kuijpers MJ, van der Meijden PE, Cosemans JM, Feijge MA, Nieswandt B, Heemskerk JW
JournalJ Biol Chem
PubMed ID17210570
Protein kinase C (PKC) isoforms regulate many platelet responses in a still incompletely understood manner. Here we investigated the roles of PKC in the platelet reactions implicated in thrombus formation as follows: secretion aggregate formation and coagulation-stimulating activity, using inhibitors with proven activity in plasma. In human and mouse platelets, ... More
Characterization of cells with different mitochondrial membrane potential during apoptosis.
AuthorsLugli E, Troiano L, Ferraresi R, Roat E, Prada N, Nasi M, Pinti M, Cooper EL, Cossarizza A
JournalCytometry A
PubMed ID16184612
BACKGROUND: Until now, the simultaneous analysis of several parameters during apoptosis, including DNA content and mitochondrial membrane potential (DeltaPsi), has not been possible because of the spectral characteristics of the commonly used dyes. Using polychromatic flow cytometry based upon multiple laser and UV lamp excitation, we have characterized cells with ... More
Cytolytic cells induce HMGB1 release from melanoma cell lines.
AuthorsIto N, DeMarco RA, Mailliard RB, Han J, Rabinowich H, Kalinski P, Stolz DB, Zeh HJ, Lotze MT
JournalJ Leukoc Biol
PubMed ID16968820
High mobility group box 1 (HMGB1) is one of the recently defined damage-associated molecular pattern molecules, passively released from necrotic cells and secreted by activated macrophage/monocytes. Whether cytolytic cells induce HMGB1 release from tumor cells is not known. We developed a highly sensitive method for detecting intracellular HMGB1 in tumor ... More
A combinatorial code for the interaction of alpha-synuclein with membranes.
AuthorsKubo S, Nemani VM, Chalkley RJ, Anthony MD, Hattori N, Mizuno Y, Edwards RH, Fortin DL
JournalJ Biol Chem
PubMed ID16020543
Considerable genetic and pathological evidence has implicated the small, soluble protein alpha-synuclein in the pathogenesis of familial and sporadic forms of Parkinsons disease (PD). However, the precise role of alpha-synuclein in the disease process as well as its normal function remain poorly understood. We recently found that an interaction with ... More
Engineered human mesenchymal stem cells for neuroblastoma therapeutics.
AuthorsNieddu V, Piredda R, Bexell D, Barton J, Anderson J, Sebire N, Kolluri K, Janes SM, Karteris E, Sala A
JournalOncol Rep
PubMed ID31115546
'Drug-resistant neuroblastoma remains a major challenge in paediatric oncology and novel and less toxic therapeutic approaches are urgently needed to improve survival and reduce the side effects of traditional therapeutic interventions. Mesenchymal stem cells (MSCs) are an attractive candidate for cell and gene therapy since they are recruited by and ... More
A Hypoxia-Inducible HIF1-GAL3ST1-Sulfatide Axis Enhances ccRCC Immune Evasion via Increased Tumor Cell-Platelet Binding.
AuthorsRobinson CM, Poon BPK, Kano Y, Pluthero FG, Kahr WHA, Ohh M
JournalMol Cancer Res
PubMed ID31427440
Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer and the major cause of mortality for individuals with von Hippel-Lindau (VHL) disease. ccRCC is characterized most frequently by inactivation of VHL tumor suppressor protein that mediates degradation of the alpha subunit of the hypoxia-inducible factor ... More