Biocompatibility, endocytosis, and intracellular trafficking of mesoporous silica and polystyrene nanoparticles in ovarian cancer cells: effects of size and surface charge groups.
AuthorsEkkapongpisit M, Giovia A, Follo C, Caputo G, Isidoro C,
JournalInt J Nanomedicine
PubMed ID22904626
Nanoparticles engineered to carry both a chemotherapeutic drug and a sensitive imaging probe are valid tools for early detection of cancer cells and to monitor the cytotoxic effects of anticancer treatment simultaneously. Here we report on the effect of size (10-30 nm versus 50 nm), type of material (mesoporous silica ... More
Induction of autophagy and cell death by tamoxifen in cultured retinal pigment epithelial and photoreceptor cells.
AuthorsCho KS, Yoon YH, Choi JA, Lee SJ, Koh JY,
JournalInvest Ophthalmol Vis Sci
PubMed ID22786900
We investigated the mechanism of tamoxifen (TAM) retinotoxicity using human retinal pigment epithelial (RPE)-derived (ARPE-19) and photoreceptor-derived (661W) cells. Cultured ARPE-19 and 661W cells were treated with 5 to 10 µM TAM, and the resultant cell death was quantified using lactate dehydrogenase (LDH) release assay. Cellular oxidative stress was determined ... More
Regulation of endocytosis via the oxygen-sensing pathway.
AuthorsWang Y, Roche O, Yan MS, Finak G, Evans AJ, Metcalf JL, Hast BE, Hanna SC, Wondergem B, Furge KA, Irwin MS, Kim WY, Teh BT, Grinstein S, Park M, Marsden PA, Ohh M,
JournalNat Med
PubMed ID19252501
'Tumor hypoxia is associated with disease progression, resistance to conventional cancer therapies and poor prognosis. Hypoxia, by largely unknown mechanisms, leads to deregulated accumulation of and signaling via receptor tyrosine kinases (RTKs) that are critical for driving oncogenesis. Here, we show that hypoxia or loss of von Hippel-Lindau protein--the principal ... More
Quantitative measurement of mast cell degranulation using a novel flow cytometric annexin-V binding assay.
AuthorsDemo SD, Masuda E, Rossi AB, Throndset BT, Gerard AL, Chan EH, Armstrong RJ, Fox BP, Lorens JB, Payan DG, Scheller RH, Fisher JM
JournalCytometry
PubMed ID10404150
'BACKGROUND: Mast cells are primary mediators of allergic inflammation. Antigen-mediated crosslinking of their cell surface immunoglobulin E (IgE) receptors results in degranulation and the release of proinflammatory mediators including histamine, tumor necrosis factor-alpha, and leukotrienes. METHODS: Mast cells were stimulated to degranulate by using either IgE crosslinking or ionophore treatment. ... More
Inhibition of the vacuolar H(+)-pump with bafilomycin A1 does not induce acrosome reaction or activate proacrosin in mouse spermatozoa.
AuthorsCodelia VA, Cortes CJ, Moreno RD
JournalBiochem Biophys Res Commun
PubMed ID16236270
'Acrosomal protease activation is regarded as an important event triggered by acrosomal reaction and leading to sperm passage through zona pellucida. Mammalian acrosome has an internal acid pH that probably helps to maintain inactive proenzymes that otherwise could be precociously activated and prevent normal fertilization. In this work, we have ... More
Transmembrane molecular pump activity of Niemann-Pick C1 protein.
AuthorsDavies JP, Chen FW, Ioannou YA
JournalScience
PubMed ID11125140
'Niemann-Pick C1 (NPC1) disease is characterized by cholesterol accumulation in lysosomes and aberrant feedback regulation of cellular cholesterol homeostasis. We provide evidence that the NPC1 protein has homology with the resistance-nodulation-division (RND) family of prokaryotic permeases and may normally function as a transmembrane efflux pump. Studies of acriflavine loading in ... More
Golgi fragmentation occurs in the cells with prefibrillar alpha-synuclein aggregates and precedes the formation of fibrillar inclusion.
AuthorsGosavi N, Lee HJ, Lee JS, Patel S, Lee SJ
JournalJ Biol Chem
PubMed ID12351643
'Amyloid-like fibrillar aggregates of intracellular proteins are common pathological features of human neurodegenerative diseases. However, the nature of pathogenic aggregates and the biological consequences of their formation remain elusive. Here, we describe (i) a model cellular system in which prefibrillar alpha-synuclein aggregates and fibrillar inclusions are naturally formed in the ... More
Visualization of G protein-coupled receptor trafficking with the aid of the green fluorescent protein. Endocytosis and recycling of cholecystokinin receptor type A.
AuthorsTarasova NI, Stauber RH, Choi JK, Hudson EA, Czerwinski G, Miller JL, Pavlakis GN, Michejda CJ, Wank SA
JournalJ Biol Chem
PubMed ID9169450
'A chimeric protein consisting of the cholecystokinin receptor type A (CCKAR) and the green fluorescent protein (GFP) was used for studying receptor localization, internalization, and recycling in live cells in real time in four different cell lines. Fusion of the C terminus of the CCKAR to the N terminus of ... More
Messenger-specific role for nicotinic acid adenine dinucleotide phosphate in neuronal differentiation.
AuthorsBrailoiu E, Churamani D, Pandey V, Brailoiu GC, Tuluc F, Patel S, Dun NJ
JournalJ Biol Chem
PubMed ID16595650
'Cells possess several Ca2+-mobilizing messengers, which couple stimulation at the cell surface by a multitude of extracellular cues to the regulation of intracellular Ca2+-sensitive targets. Recent studies suggest that agonists differentially select from this molecular palette to generate their characteristic Ca2+ signals but it is still unclear whether different messengers ... More
Interfacial sensing by alveolar type II cells: a new concept in lung physiology?
AuthorsRavasio A, Hobi N, Bertocchi C, Jesacher A, Dietl P, Haller T,
JournalAm J Physiol Cell Physiol
PubMed ID21270294
'Alveolar type II (AT II) cells are in close contact with an air-liquid interface (I(AL)). This contact may be of considerable physiological relevance; however, no data exist to provide a satisfying description of this specific microenvironment. This is mainly due to the experimental difficulty to manipulate and analyze cell-air contacts ... More
Quantitative comparison of intracellular unpacking kinetics of polyplexes by a model constructed from quantum dot-FRET.
AuthorsChen HH, Ho YP, Jiang X, Mao HQ, Wang TH, Leong KW,
JournalMol Ther
PubMed ID18180773
'A major challenge for non-viral gene delivery is gaining a mechanistic understanding of the rate-limiting steps. A critical barrier in polyplex-mediated gene delivery is the timely unpacking of polyplexes within the target cell to liberate DNA for efficient gene transfer. In this study, the component plasmid DNA and polymeric gene ... More
Inositol trisphosphate and cyclic ADP-ribose-mediated release of Ca2+ from single isolated pancreatic zymogen granules.
'In pancreatic acinar cells low (physiological) agonist concentrations evoke cytosolic Ca2+ spikes specifically in the apical secretory pole that contains a high density of secretory (zymogen) granules (ZGs). Inositol 1,4,5-trisphosphate (IP3) is believed to release Ca2+ from the endoplasmic reticulum, but we have now tested whether the Ca(2+)-releasing messengers IP3 ... More
Enhanced lysosomal activity is involved in Bax inhibitor-1-induced regulation of the endoplasmic reticulum (ER) stress response and cell death against ER stress: involvement of vacuolar H+-ATPase (V-ATPase).
AuthorsLee GH, Kim DS, Kim HT, Lee JW, Chung CH, Ahn T, Lim JM, Kim IK, Chae HJ, Kim HR,
JournalJ Biol Chem
PubMed ID21586565
'Bax inhibitor-1 (BI-1) is an evolutionarily conserved protein that protects cells against endoplasmic reticulum (ER) stress while also affecting the ER stress response. In this study, we examined BI-1-induced regulation of the ER stress response as well as the control of the protein over cell death under ER stress. In ... More
Lysosomal membrane permeabilization is an early event in Sigma-2 receptor ligand mediated cell death in pancreatic cancer.
'Sigma-2 receptor ligands have been studied for treatment of pancreatic cancer because they are preferentially internalized by proliferating cells and induce apoptosis. This mechanism of apoptosis is poorly understood, with varying reports of caspase-3 dependence. We evaluated multiple sigma-2 receptor ligands in this study, each shown to decrease tumor burden ... More
Fluorescence and multiphoton imaging resolve unique structural forms of sterol in membranes of living cells.
'Although cholesterol is an essential component of mammalian membranes, resolution of cholesterol organization in membranes and organelles (i.e. lysosomes) of living cells is hampered by the paucity of nondestructive, nonperturbing methods providing real time structural information. Advantage was taken of the fact that the emission maxima of a naturally occurring ... More
The lysosomal compartment as intracellular calcium store in MDCK cells: a possible involvement in InsP3-mediated Ca2+ release.
AuthorsHaller T, Dietl P, Deetjen P, Völkl H
JournalCell Calcium
PubMed ID8689673
'To test for a possible role of lysosomes in intracellular Ca2+ homeostasis, the effects of glycyl-L-phenylalanine-beta-naphthylamide (GPN), known to permeabilize these organelles by osmotic swelling, were studied in single MDCK cells. Fluorescence of acridine orange, rhodol green dextran, lysotracker green and FITC-dextran indicated that GPN (0.2 mmol/l) elicited a reversible ... More
Analysis of retrograde transport in motor neurons reveals common endocytic carriers for tetanus toxin and neurotrophin receptor p75NTR.
AuthorsLalli G, Schiavo G
JournalJ Cell Biol
PubMed ID11807088
'Axonal retrograde transport is essential for neuronal growth and survival. However, the nature and dynamics of the membrane compartments involved in this process are poorly characterized. To shed light on this pathway, we established an experimental system for the visualization and the quantitative study of retrograde transport in living motor ... More
H-type dimer formation of fluorophores: a mechanism for activatable, in vivo optical molecular imaging.
AuthorsOgawa M, Kosaka N, Choyke PL, Kobayashi H,
JournalACS Chem Biol
PubMed ID19480464
'In vivo molecular imaging with target-specific activatable '
Glycolipid antigen processing for presentation by CD1d molecules.
AuthorsPrigozy TI, Naidenko O, Qasba P, Elewaut D, Brossay L, Khurana A, Natori T, Koezuka Y, Kulkarni A, Kronenberg M
JournalScience
PubMed ID11158680
'The requirement for processing glycolipid antigens in T cell recognition was examined with mouse CD1d-mediated responses to glycosphingolipids (GSLs). Although some disaccharide GSL antigens can be recognized without processing, the responses to three other antigens, including the disaccharide GSL Gal(alpha1-->2)GalCer (Gal, galactose; GalCer, galactosylceramide), required removal of the terminal sugars ... More
FTY720 increases CD74 expression and sensitizes mantle cell lymphoma cells to milatuzumab-mediated cell death.
AuthorsAlinari L, Mahoney E, Patton J, Zhang X, Huynh L, Earl CT, Mani R, Mao Y, Yu B, Quinion C, Towns WH, Chen CS, Goldenberg DM, Blum KA, Byrd JC, Muthusamy N, Praetorius-Ibba M, Baiocchi RA,
JournalBlood
PubMed ID22042694
'Mantle cell lymphoma (MCL) is an aggressive B-cell malignancy with a short median survival despite multimodal therapy. FTY720, an immunosuppressive drug approved for the treatment of multiple sclerosis, promotes MCL cell death concurrent with down-modulation of phospho-Akt and cyclin D1 and subsequent cell-cycle arrest. However, the mechanism of FTY720-mediated MCL ... More
Prion peptide 106-126 modulates the aggregation of cellular prion protein and induces the synthesis of potentially neurotoxic transmembrane PrP.
AuthorsGu Y, Fujioka H, Mishra RS, Li R, Singh N
JournalJ Biol Chem
PubMed ID11682469
'In infectious and familial prion disorders, neurodegeneration is often seen without obvious deposits of the scrapie prion protein (PrP(Sc)), the principal cause of neuronal death in prion disorders. In such cases, neurotoxicity must be mediated by alternative pathways of cell death. One such pathway is through a transmembrane form of ... More
Compound exocytosis and cumulative fusion in eosinophils.
AuthorsHafez I, Stolpe A, Lindau M
JournalJ Biol Chem
PubMed ID12923203
'Focal release of cytotoxic proteins by eosinophils onto the target surface plays an important role in parasite killing. Degranulation was stimulated by intracellular application of calcium and guanosine 5''-3-O-(thio)triphosphate via the recording patch pipette or via streptolysin-O permeabilization. Exocytotic fusion was monitored by capacitance measurements, whereas release of fluorescent weak ... More
Receptor-mediated endocytosis of phosphodiester oligonucleotides in the HepG2 cell line: evidence for non-conventional intracellular trafficking.
Authorsde Diesbach P, N'Kuli F, Berens C, Sonveaux E, Monsigny M, Roche AC, Courtoy PJ
JournalNucleic Acids Res
PubMed ID11917011
'Having identified an oligonucleotide (ON) receptor in the HepG2 cell line, we have re-examined here the kinetics of ON uptake, subcellular distribution and intracellular localisation in these cells, at concentrations relevant for the study of a receptor-dependent process. Kinetic parameters of ON endocytosis were comparable with those of the receptor-mediated ... More
Macrophages present pinocytosed exogenous antigen via MHC class I whereas antigen ingested by receptor-mediated endocytosis is presented via MHC class II.
AuthorsPeppelenbosch MP, DeSmedt M, Pynaert G, van Deventer SJ, Grooten J
JournalJ Immunol
PubMed ID10925281
'Macrophages present exogenous Ag either via MHC class I or MHC class II molecules. We investigated whether the mode of hemagglutinin (HA) uptake influences the class of MHC molecule by which this Ag is presented. Normally, HA is ingested by receptor-mediated endocytosis, but this may be switched to macropinocytosis and ... More
Leukotoxin (Leukothera®) targets active leukocyte function antigen-1 (LFA-1) protein and triggers a lysosomal mediated cell death pathway.
AuthorsDiFranco KM, Gupta A, Galusha LE, Perez J, Nguyen TV, Fineza CD, Kachlany SC,
JournalJ Biol Chem
PubMed ID22467872
'Leukotoxin (LtxA) is a protein toxin that is secreted from the oral bacterium, Aggregatibacter actinomycetemcomitans. LtxA targets specifically the ß(2) integrin, leukocyte function antigen-1 (LFA-1) on white blood cells (WBCs) and causes cell death. LtxA preferentially targets activated WBCs and is being developed as a therapeutic agent for the treatment ... More
ZnT-2, a mammalian protein that confers resistance to zinc by facilitating vesicular sequestration.
AuthorsPalmiter RD, Cole TB, Findley SD
JournalEMBO J
PubMed ID8617223
'A cDNA encoding a second zinc transporter (ZnT-2) was isolated from a rat kidney cDNA expression library by complementation of a zinc-sensitive BHK cell line. The protein predicted from the open reading frame of ZnT-2 cDNA has 359 amino acids and initiates with a CTG codon. It resembles ZnT-1 (a ... More
Labeling and exocytosis of secretory compartments in RBL mastocytes by polystyrene and mesoporous silica nanoparticles.
AuthorsEkkapongpisit M, Giovia A, Nicotra G, Ozzano M, Caputo G, Isidoro C,
JournalInt J Nanomedicine
PubMed ID22605932
'For a safe ''in vivo'' biomedical utilization of nanoparticles, it is essential to assess not only biocompatibility, but also the potential to trigger unwanted side effects at both cellular and tissue levels. Mastocytes (cells having secretory granules containing cytokines, vasoactive amine, and proteases) play a pivotal role in the immune ... More
Live intracellular super-resolution imaging using site-specific stains.
AuthorsCarlini L, Manley S,
Journal
PubMed ID24079385
'Point localization super-resolution imaging (SR) requires dyes that can cycle between fluorescent and dark states, in order for their molecular positions to be localized and create a reconstructed image. Dyes should also densely decorate biological features of interest to fully reveal structures being imaged. We tested site-specific dyes in several ... More
Tobacco calmodulin-like protein provides secondary defense by binding to and directing degradation of virus RNA silencing suppressors.
AuthorsNakahara KS, Masuta C, Yamada S, Shimura H, Kashihara Y, Wada TS, Meguro A, Goto K, Tadamura K, Sueda K, Sekiguchi T, Shao J, Itchoda N, Matsumura T, Igarashi M, Ito K, Carthew RW, Uyeda I,
JournalProc Natl Acad Sci U S A
PubMed ID22665793
'RNA silencing (RNAi) induced by virus-derived double-stranded RNA (dsRNA), which is in a sense regarded as a pathogen-associated molecular pattern (PAMP) of viruses, is a general plant defense mechanism. To counteract this defense, plant viruses express RNA silencing suppressors (RSSs), many of which bind to dsRNA and attenuate RNAi. We ... More
[Ca(2+)](i) oscillations regulate type II cell exocytosis in the pulmonary alveolus.
AuthorsAshino Y, Ying X, Dobbs LG, Bhattacharya J
JournalAm J Physiol Lung Cell Mol Physiol
PubMed ID10893197
'Pulmonary surfactant, a critical determinant of alveolar stability, is secreted by alveolar type II cells by exocytosis of lamellar bodies (LBs). To determine exocytosis mechanisms in situ, we imaged single alveolar cells from the isolated blood-perfused rat lung. We quantified cytosolic Ca(2+) concentration ([Ca(2+)](i)) by the fura 2 method and ... More
Suicidal membrane repair regulates phosphatidylserine externalization during apoptosis.
One of the hallmarks of apoptosis is the redistribution of phosphatidylserine (PS) from the inner-to-outer plasma membrane (PM) leaflet, where it functions as a ligand for phagocyte recognition and the suppression of inflammatory responses. The mechanism by which apoptotic cells externalize PS has been assumed to involve ... More
Real-time imaging of astrocyte response to quantum dots: in vivo screening model system for biocompatibility of nanoparticles.
AuthorsMaysinger D, Behrendt M, Lalancette-Hébert M, Kriz J
JournalNano Lett
PubMed ID17638392
Astrocytes are the principle macroglial brain cells. They are activated by different stressors and brain injuries. Quantum dots (QDs) can cause oxidative stress. This study shows a real-time imaging of primary cortical cultures and assessment of QD-induced activation of astrocytes in the brains of transgenic mice with the luciferase gene ... More
Micellar nanocontainers distribute to defined cytoplasmic organelles.
AuthorsSavic R, Luo L, Eisenberg A, Maysinger D
JournalScience
PubMed ID12714738
Block copolymer micelles are water-soluble biocompatible nanocontainers with great potential for delivering hydrophobic drugs. An understanding of their cellular distribution is essential to achieving selective delivery of drugs at the subcellular level. Triple-labeling confocal microscopy in live cells revealed the localization of micelles in several cytoplasmic organelles, including mitochondria, but ... More
Decreased uptake of bodipy-labelled compounds in the presence of the nuclear stain, DRAQ5.
AuthorsSnyder DS, Garon CF
JournalJ Microsc
PubMed ID12950469
We have found the nuclear stain DRAQ5 to decrease the cellular uptake of a series of boron dipyrromethane (bodipy)-labelled compounds. This phenomenon is consistent between Lysotracker Green DND 26, Lysotracker Red DND 99 and bodipy-labelled mycolactone. Although DRAQ5 uptake was not prevented, DRAQ5 was in significant excess in each case. ... More
Nanotubular highways for intercellular organelle transport.
AuthorsRustom A, Saffrich R, Markovic I, Walther P, Gerdes HH
JournalScience
PubMed ID14963329
Cell-to-cell communication is a crucial prerequisite for the development and maintenance of multicellular organisms. To date, diverse mechanisms of intercellular exchange of information have been documented, including chemical synapses, gap junctions, and plasmodesmata. Here, we describe highly sensitive nanotubular structures formed de novo between cells that create complex networks. These ... More
Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen.
Small molecules that perturb specific protein functions are valuable tools for dissecting complex processes in mammalian cells. A combination of two phenotype-based screens, one based on a specific posttranslational modification, the other visualizing microtubules and chromatin, was used to identify compounds that affect mitosis. One compound, here named monastrol, arrested ... More
Cathepsin B controls the persistence of memory CD8+ T lymphocytes.
AuthorsByrne SM, Aucher A, Alyahya S, Elder M, Olson ST, Davis DM, Ashton-Rickardt PG,
JournalJ Immunol
PubMed ID22745374
The persistence of memory T lymphocytes confers lifelong protection from pathogens. Memory T cells survive and undergo homeostatic proliferation (HSP) in the absence of Ag, although the cell-intrinsic mechanisms by which cytokines drive the HSP of memory T cells are not well understood. In this study we report that lysosome ... More
Lysosomal transmembrane protein LAPTM4B promotes autophagy and tolerance to metabolic stress in cancer cells.
AuthorsLi Y, Zhang Q, Tian R, Wang Q, Zhao JJ, Iglehart JD, Wang ZC, Richardson AL,
JournalCancer Res
PubMed ID22037872
Amplification of chromosome 8q22, which includes the gene for lysosomal associated transmembrane protein LAPTM4B, has been linked to de novo anthracycline resistance in primary breast cancers with poor prognosis. LAPTM4B overexpression can induce cytosolic retention of anthracyclines and decrease drug-induced DNA damage. In this study, we tested the hypothesis that ... More
Involvement of autophagy in oncogenic K-Ras-induced malignant cell transformation.
AuthorsKim MJ, Woo SJ, Yoon CH, Lee JS, An S, Choi YH, Hwang SG, Yoon G, Lee SJ,
JournalJ Biol Chem
PubMed ID21300795
Autophagy has recently been implicated in both the prevention and progression of cancer. However, the molecular basis for the relationship between autophagy induction and the initial acquisition of malignancy is currently unknown. Here, we provide the first evidence that autophagy is essential for oncogenic K-Ras (K-Ras(V12))-induced malignant cell transformation. Retroviral ... More
Induction of lysosomal dilatation, arrested autophagy, and cell death by chloroquine in cultured ARPE-19 cells.
AuthorsYoon YH, Cho KS, Hwang JJ, Lee SJ, Choi JA, Koh JY,
JournalInvest Ophthalmol Vis Sci
PubMed ID20574031
To characterize and investigate the mechanism of chloroquine (CQ) retinotoxicity in human retinal pigment epithelium-derived ARPE-19 cells. Cultured ARPE-19 cells were exposed to 10 to 250 µM CQ, and cell death was quantified using a lactate dehydrogenase release assay. Autophagy was studied in ARPE-19 cells transfected with GFP-LC3. Lysosomes in ... More
Deficiency of ATP13A2 leads to lysosomal dysfunction, a-synuclein accumulation, and neurotoxicity.
AuthorsUsenovic M, Tresse E, Mazzulli JR, Taylor JP, Krainc D,
JournalJ Neurosci
PubMed ID22442086
The autophagy-lysosomal pathway plays an important role in the clearance of long-lived proteins and dysfunctional organelles. Lysosomal dysfunction has been implicated in several neurodegenerative disorders including Parkinson's disease and related synucleinopathies that are characterized by accumulations of a-synuclein in Lewy bodies. Recent identification of mutations in genes linked to lysosomal ... More
Tafenoquine, an antiplasmodial 8-aminoquinoline, targets leishmania respiratory complex III and induces apoptosis.
Tafenoquine (TFQ), an 8-aminoquinoline analogue of primaquine, which is currently under clinical trial (phase IIb/III) for the treatment and prevention of malaria, may represent an alternative treatment for leishmaniasis. In this work, we have studied the mechanism of action of TFQ against Leishmania parasites. TFQ impaired the overall bioenergetic metabolism ... More
Stable synthetic bacteriochlorins overcome the resistance of melanoma to photodynamic therapy.
AuthorsMroz P, Huang YY, Szokalska A, Zhiyentayev T, Janjua S, Nifli AP, Sherwood ME, Ruzié C, Borbas KE, Fan D, Krayer M, Balasubramanian T, Yang E, Kee HL, Kirmaier C, Diers JR, Bocian DF, Holten D, Lindsey JS, Hamblin MR,
JournalFASEB J
PubMed ID20385618
Cutaneous malignant melanoma remains a therapeutic challenge, and patients with advanced disease have limited survival. Photodynamic therapy (PDT) has been successfully used to treat many malignancies, and it may show promise as an antimelanoma modality. However, high melanin levels in melanomas can adversely affect PDT effectiveness. Herein the extent of ... More
Leucine-rich repeat kinase 2 regulates autophagy through a calcium-dependent pathway involving NAADP.
Mutations in the leucine-rich repeat kinase-2 (LRRK2) gene cause late-onset Parkinson's disease, but its physiological function has remained largely unknown. Here we report that LRRK2 activates a calcium-dependent protein kinase kinase-ß (CaMKK-ß)/adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway which is followed by a persistent increase in autophagosome formation. Simultaneously, LRKR2 ... More
Cysteine Cathepsins Trigger Caspase-dependent Cell Death through Cleavage of Bid and Antiapoptotic Bcl-2 Homologues.
AuthorsDroga-Mazovec G, Bojic L, Petelin A, Ivanova S, Romih R, Repnik U, Salvesen GS, Stoka V, Turk V, Turk B,
JournalJ Biol Chem
PubMed ID18469004
As a model for defining the role of lysosomal cathepsins in apoptosis, we characterized the action of the lysosomotropic agent LeuLeuOMe using distinct cellular models. LeuLeuOMe induces lysosomal membrane permeabilization, resulting in release of lysosomal cathepsins that cleave the proapoptotic Bcl-2 family member Bid and degrade the antiapoptotic member Bcl-2, ... More
Determining the distribution of probes between different subcellular locations through automated unmixing of subcellular patterns.
Many proteins or other biological macromolecules are localized to more than one subcellular structure. The fraction of a protein in different cellular compartments is often measured by colocalization with organelle-specific fluorescent markers, requiring availability of fluorescent probes for each compartment and acquisition of images for each in conjunction with the ... More
Increased glycolytic ATP synthesis is associated with tafenoquine resistance in Leishmania major.
AuthorsManzano JI, Carvalho L, Pérez-Victoria JM, Castanys S, Gamarro F,
JournalAntimicrob Agents Chemother
PubMed ID21199921
Tafenoquine (TFQ), an 8-aminoquinoline used to treat and prevent Plasmodium infections, could represent an alternative therapy for leishmaniasis. Indeed, TFQ has shown significant leishmanicidal activity both in vitro and in vivo, where it targets Leishmania mitochondria and activates a final apoptosis-like process. In order not to jeopardize the life span ... More
ApoE promotes the proteolytic degradation of Abeta.
AuthorsJiang Q, Lee CY, Mandrekar S, Wilkinson B, Cramer P, Zelcer N, Mann K, Lamb B, Willson TM, Collins JL, Richardson JC, Smith JD, Comery TA, Riddell D, Holtzman DM, Tontonoz P, Landreth GE,
JournalNeuron
PubMed ID18549781
Apolipoprotein E is associated with age-related risk for Alzheimer's disease and plays critical roles in Abeta homeostasis. We report that ApoE plays a role in facilitating the proteolytic clearance of soluble Abeta from the brain. The endolytic degradation of Abeta peptides within microglia by neprilysin and related enzymes is dramatically ... More
Spreading of neurodegenerative pathology via neuron-to-neuron transmission of ß-amyloid.
Alzheimer's disease (AD) is the major cause of dementia. During the development of AD, neurofibrillary tangles progress in a fixed pattern, starting in the transentorhinal cortex followed by the hippocampus and cortical areas. In contrast, the deposition of ß-amyloid (Aß) plaques, which are the other histological hallmark of AD, does ... More
The utilization of pathogen-like cellular trafficking by single chain block copolymer.
Amphiphilic triblock copolymer, poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide), Pluronic P85, is unexpectedly shown to utilize sophisticated cellular trafficking mechanisms and enter brain microvessel endothelial cells and primary neurons that are poorly penetrable. Though caveolae serve as a primary entry site for the copolymer single chains, in cells devoid of caveolae, the ... More
In situ detection of starvation-induced autophagy.
AuthorsMartinet W, De Meyer GR, Andries L, Herman AG, Kockx MM,
JournalJ Histochem Cytochem
PubMed ID16148314
Autophagy is a regulated bulk degradation process involved in many different human pathologies. Transmission electron microscopy (TEM) is currently the only reliable method for monitoring autophagy in situ. Because TEM is labor intensive, we questioned whether useful marker proteins can be found for unambiguous detection of autophagy in tissue via ... More
Glycolipid trafficking in Drosophila undergoes pathway switching in response to aberrant cholesterol levels.
AuthorsHortsch R, Lee E, Erathodiyil N, Hebbar S, Steinert S, Lee JY, Chua DS, Kraut R,
JournalMol Biol Cell
PubMed ID20053687
In lipid storage diseases, the intracellular trafficking of sphingolipids is altered by conditions of aberrant cholesterol accumulation. Drosophila has been used recently to model lipid storage diseases, but the effects of sterol accumulation on sphingolipid trafficking are not known in the fly, and the trafficking of sphingolipids in general has ... More
The NALP3 inflammasome is involved in the innate immune response to amyloid-beta.
AuthorsHalle A, Hornung V, Petzold GC, Stewart CR, Monks BG, Reinheckel T, Fitzgerald KA, Latz E, Moore KJ, Golenbock DT,
JournalNat Immunol
PubMed ID18604209
The fibrillar peptide amyloid-beta (A beta) has a chief function in the pathogenesis of Alzheimer's disease. Interleukin 1 beta (IL-1 beta) is a key cytokine in the inflammatory response to A beta. Insoluble materials such as crystals activate the inflammasome formed by the cytoplasmic receptor NALP3, which results in the ... More
Bioinformatic and image analyses of the cellular localization of the apoptotic proteins endonuclease G, AIF, and AMID during apoptosis in human cells.
AuthorsVarecha M, Amrichová J, Zimmermann M, Ulman V, Lukásová E, Kozubek M
JournalApoptosis
PubMed ID17347867
We studied the cellular localization of the apoptotic proteins endonuclease G, AIF, and AMID in silico using three prediction tools and in living cells using both single-cell colocalization image analysis and nuclear translocation analysis. We confirmed the mitochondrial localization of endonuclease G and AIF by prediction analysis and by single-cell ... More
Dynein is required for receptor sorting and the morphogenesis of early endosomes.
AuthorsDriskell OJ, Mironov A, Allan VJ, Woodman PG
JournalNat Cell Biol
PubMed ID17173037
The early endosome is organised into domains to ensure the separation of cargo. Activated mitogenic receptors, such as epidermal growth factor (EGF) receptor, are concentrated into vacuoles enriched for the small GTPase Rab5, which progressively exclude nutrient receptors, such as transferrin receptor, into neighbouring tubules. These vacuoles become enlarged, increase ... More
Lysosomal destabilization contributes to apoptosis of germinal center B-lymphocytes.
Authorsvan Nierop K, Muller FJ, Stap J, Van Noorden CJ, van Eijk M, de Groot C
JournalJ Histochem Cytochem
PubMed ID16957167
During germinal center (GC) reactions, B-lymphocytes with high-affinity B-cell receptors are selected. Regulation of apoptosis is a key process in selecting such wanted B-cells and in eliminating B-cells with unwanted specificities. In this paper, we show that apoptosis in human GC B-cells involves lysosomal destabilization, which is strictly controlled by ... More
Block copolymers modify the internalization of micelle-incorporated probes into neural cells.
AuthorsMaysinger D, Berezovska O, Savic R, Soo PL, Eisenberg A
JournalBiochim Biophys Acta
PubMed ID11420118
An important therapeutic concern is rate and extent of internalization of drugs into cells. Hydrophilic agents often internalize poorly and slowly, and highly lipophilic ones too rapidly. The incorporation of drugs into micelles allows regulation of their internalization parameters, and newly-described block copolymers can be selectively tailored to suit specific ... More
Analysis of Na+,K+-ATPase motion and incorporation into the plasma membrane in response to G protein-coupled receptor signals in living cells.
AuthorsBertorello AM, Komarova Y, Smith K, Leibiger IB, Efendiev R, Pedemonte CH, Borisy G, Sznajder JI
JournalMol Biol Cell
PubMed ID12631730
Dopamine (DA) increases Na(+),K(+)-ATPase activity in lung alveolar epithelial cells. This effect is associated with an increase in Na(+),K(+)-ATPase molecules within the plasma membrane (). Analysis of Na(+),K(+)-ATPase motion was performed in real-time in alveolar cells stably expressing Na(+),K(+)-ATPase molecules carrying a fluorescent tag (green fluorescent protein) in the alpha-subunit. ... More
Localised and rapid Ca2+ micro-events in human neutrophils: conventional Ca2+ puffs and global waves without peripheral-restriction or wave cycling.
AuthorsHillson EJ, Hallett MB
JournalCell Calcium
PubMed ID17324458
Ultra-localised and peripherally restricted zones of elevated Ca2+ (z-waves) have been reported to cycle around the periphery of neutrophils at low frequency (1/20s) in the absence of conventional localised Ca2+ (puffs) and global Ca2+ (waves) signals. However, we report here that fast confocal laser scanning of human neutrophils loaded with ... More
Noninvasive two-photon imaging reveals retinyl ester storage structures in the eye.
AuthorsImanishi Y, Batten ML, Piston DW, Baehr W, Palczewski K
JournalJ Cell Biol
PubMed ID14745001
Visual sensation in vertebrates is triggered when light strikes retinal photoreceptor cells causing photoisomerization of the rhodopsin chromophore 11-cis-retinal to all-trans-retinal. The regeneration of preillumination conditions of the photoreceptor cells requires formation of 11-cis-retinal in the adjacent retinal pigment epithelium (RPE). Using the intrinsic fluorescence of all-trans-retinyl esters, noninvasive two-photon ... More
Intracellular and extracellular leukemia inhibitory factor proteins have different cellular activities that are mediated by distinct protein motifs.
AuthorsHaines BP, Voyle RB, Rathjen PD
JournalMol Biol Cell
PubMed ID10749936
Although many growth factors and cytokines have been shown to be localized within the cell and nucleus, the mechanism by which these molecules elicit a biological response is not well understood. The cytokine leukemia inhibitory factor (LIF) provides a tractable experimental system to investigate this problem, because translation of alternatively ... More
C11-BODIPY(581/591), an oxidation-sensitive fluorescent lipid peroxidation probe: (micro)spectroscopic characterization and validation of methodology.
AuthorsDrummen GP, van Liebergen LC, Op den Kamp JA, Post JA
JournalFree Radic Biol Med
PubMed ID12160930
C11-BODIPY(581/591) is a fluorescent radio-probe for indexing lipid peroxidation and antioxidant efficacy in model membrane systems and living cells, with excellent characteristics: (i) emission in the visible range of the electromagnetic spectrum, with good spectral separation of the nonoxidized (595 nm) and oxidized (520 nm) forms; (ii) has a high ... More
Rhodamine B, a fluorescent probe for acidic organelles in denervated skeletal muscle.
AuthorsVult von Steyern F, Josefsson JO, Tågerud S
JournalJ Histochem Cytochem
PubMed ID8648087
We describe a very efficient method for fluorescent labeling of acidic structures in denervated skeletal muscle with rhodamine B. Rhodamine B at 50 ng/ml gave selective and distinct segmental labeling of denervated muscle fibers after 5-min incubation at room temperature. Labeling was also achieved at 4 degrees C. The labeling ... More
Peroxisomal ghosts are intracellular structures distinct from lysosomal compartments in Zellweger syndrome: a confocal laser scanning microscopy study.
Peroxisome ghosts are aberrant peroxisomal structures found in cultured skin fibroblasts from patients affected by Zellweger Syndrome (ZS), a genetic disorder of peroxisomal assembly. They contain peroxisomal integral membrane proteins (PxIMPs) and they lack most of the matrix enzymes that should be inside the organelle (Santos et al., Science 239 ... More
The Golgi apparatus segregates from the lysosomal/acrosomal vesicle during rhesus spermiogenesis: structural alterations.
AuthorsMoreno RD, Ramalho-Santos J, Chan EK, Wessel GM, Schatten G
JournalDev Biol
PubMed ID10694426
The acrosome is an acidic secretory vesicle containing hydrolytic enzymes that are involved in the sperm's passage across the zona pellucida. Imaging of the acrosomal vesicle and the Golgi apparatus in live rhesus monkey spermatids was accomplished by using the vital fluorescent probe LysoTracker DND-26. Concurrently, the dynamics of living ... More
A fluorescent microplate assay for exocytosis in alveolar type II cells.
AuthorsWemhöner A, Frick M, Dietl P, Jennings P, Haller T
JournalJ Biomol Screen
PubMed ID16699129
The authors describe a simple, reliable, and quantitative assay to monitor exocytotic fusion of lamellar bodies (LBs) in adherent rat alveolar type II (AT II) cells. The assay is based on fluorescence measurements of LB-plasma membrane (PM) fusions modified for the use in multiwell culture plates to obtain a high-sample ... More
Separate roles for the Golgi apparatus and lysosomes in the sequestration of drugs in the multidrug-resistant human leukemic cell line HL-60.
AuthorsGong Y, Duvvuri M, Krise JP
JournalJ Biol Chem
PubMed ID14522995
The sequestration of drugs away from cellular target sites into cytoplasmic organelles of multidrug-resistant (MDR) cancer cells has been recently shown to be a cause for ineffective drug therapy. This process is poorly understood despite the fact that it has been observed in a large number of MDR cancer cell ... More
Effect of cryopreservation of bovine sperm organelle function and viability as determined by flow cytometry.
AuthorsThomas CA, Garner DL, DeJarnette JM, Marshall CE
JournalBiol Reprod
PubMed ID9510967
Flow cytometry was used to compare the functional status of fluorescently stained sperm organelles from 12 Holstein bulls after storage for 24 h at 5 degrees C and after cryopreservation. The organelle-specific stains, SYBR-14 and LysoTracker Green DND-26, identified spermatozoa with intact plasmalemma and those with intact acrosomes, respectively. The ... More
Fluorometric assessments of acrosomal integrity and viability in cryopreserved bovine spermatozoa.
AuthorsThomas CA, Garner DL, DeJarnette JM, Marshall CE
JournalBiol Reprod
PubMed ID9096883
The combination of specific fluorometric staining and flow cytometry provides a rapid and precise means of assessing the functional status of cells. We sought to utilize this approach to quantify two important seminal characteristics, acrosomal integrity and sperm viability, and to compare these with classical microscopic measurements of acrosomal integrity ... More
Calpain is required for macroautophagy in mammalian cells.
AuthorsDemarchi F, Bertoli C, Copetti T, Tanida I, Brancolini C, Eskelinen EL, Schneider C
JournalJ Cell Biol
PubMed ID17101693
Ubiquitously expressed micro- and millicalpain, which both require the calpain small 1 (CAPNS1) regulatory subunit for function, play important roles in numerous biological and pathological phenomena. We have previously shown that the product of GAS2, a gene specifically induced at growth arrest, is an inhibitor of millicalpain and that its ... More
Heterodimerization of endothelin-converting enzyme-1 isoforms regulates the subcellular distribution of this metalloprotease.
AuthorsMuller L, Barret A, Etienne E, Meidan R, Valdenaire O, Corvol P, Tougard C
JournalJ Biol Chem
PubMed ID12393864
Endothelin-converting enzyme (ECE) is a membrane metalloprotease that generates endothelin from its direct precursor big endothelin. Four isoforms of ECE-1 are produced from a single gene through the use of alternate promoters. These isoforms share the same extracellular catalytic domain and contain unique cytosolic tails, which results in their specific ... More
Control of membrane fusion during spermiogenesis and the acrosome reaction.
AuthorsRamalho-Santos J, Schatten G, Moreno RD
JournalBiol Reprod
PubMed ID12297516
Membrane fusion is important to reproduction because it occurs in several steps during the process of fertilization. Many events of intracellular trafficking occur during both spermiogenesis and oogenesis. The acrosome reaction, a key feature during mammalian fertilization, is a secretory event involving the specific fusion of the outer acrosomal membrane ... More
Comparative pathogenesis of haloacetic acid and protein kinase inhibitor embryotoxicity in mouse whole embryo culture.
AuthorsWard KW, Rogers EH, Hunter ES
JournalToxicol Sci
PubMed ID10653529
Haloacetic acids (HAs) are embryotoxic contaminants commonly found in drinking water. The mechanism of HA embryotoxicity has not been defined, but may be mediated in part by protein kinase C (PKC) inhibition. This study was conducted to evaluate the pathogenesis of HA embryotoxicity, and to compare these data with those ... More
Cholesterol oxidation switches the internalization pathway of endothelin receptor type A from caveolae to clathrin-coated pits in Chinese hamster ovary cells.
AuthorsOkamoto Y, Ninomiya H, Miwa S, Masaki T
JournalJ Biol Chem
PubMed ID10692447
We investigated the mechanism of endothelin receptor type A (ETA) internalization in Chinese hamster ovary cells using two assays; flow cytometric quantification of cell surface myc-ETA and in situ localization of Cy5-labeled ET-1. In both assays, agonist-dependent internalization of myc-ETA was inhibited by nystatin and filipin, both of which disrupt ... More
Dynamics of surfactant release in alveolar type II cells.
AuthorsHaller T, Ortmayr J, Friedrich F, Völkl H, Dietl P
JournalProc Natl Acad Sci U S A
PubMed ID9465058
Pulmonary surfactant, secreted via exocytosis of lamellar bodies (LB) by alveolar type II (AT II) cells, maintains low alveolar surface tension and is therefore essential for normal lung function. Here we describe real-time monitoring of exocytotic activity in these cells by visualizing and quantifying LB fusion with the plasma membrane ... More
Kahalalide F, a new marine-derived compound, induces oncosis in human prostate and breast cancer cells.
AuthorsSuárez Y, González L, Cuadrado A, Berciano M, Lafarga M, Muñoz A
JournalMol Cancer Ther
PubMed ID14555705
Kahalalide F (KF) is a novel antitumor drug of marine origin under clinical investigation. KF showed a potent cytotoxic activity against a panel of human prostate and breast cancer cell lines, with IC(50) ranging from 0.07 micro M (PC3) to 0.28 micro M (DU145, LNCaP, SKBR-3, BT474, MCF7). Importantly, nontumor ... More
Mutations at amino-acid 482 in the ABCG2 gene affect substrate and antagonist specificity.
AuthorsRobey RW, Honjo Y, Morisaki K, Nadjem TA, Runge S, Risbood M, Poruchynsky MS, Bates SE
JournalBr J Cancer
PubMed ID14612912
Recent studies have shown that mutations at amino-acid 482 in the ABCG2 gene affect the substrate specificity of the protein. To delineate the effects of these mutations clearly, human embryonic kidney cells (HEK-293) were stably transfected with wild-type 482R or mutant 482G and 482T ABCG2. By flow cytometry, mitoxantrone, BODIPY-prazosin, ... More
Nuclear factor-kappaB mediates up-regulation of cathepsin B by doxorubicin in tumor cells.
AuthorsBien S, Ritter CA, Gratz M, Sperker B, Sonnemann J, Beck JF, Kroemer HK
JournalMol Pharmacol
PubMed ID15102937
Anthracyclines such as doxorubicin remain among the most effective agents for the treatment of solid tumors and hematological malignancies. To overcome dose-limiting side effects like cardiotoxicity, an intensive effort has been undertaken to develop promising doxorubicin prodrugs that are specifically activated at the tumor site. One approach is the application ... More
Quantitative analysis of Pc 4 localization in mouse lymphoma (LY-R) cells via double-label confocal fluorescence microscopy.
AuthorsTrivedi NS, Wang HW, Nieminen AL, Oleinick NL, Izatt JA
JournalPhotochem Photobiol
PubMed ID10818795
Photodynamic therapy (PDT) is a novel cancer therapy that uses light-activated drugs (photosensitizers) to destroy tumor tissue. Reactive oxygen species produced during PDT are thought to cause the destruction of tumor tissue. However, the precise mechanism of PDT is not completely understood. To provide insight into the in vitro mechanisms ... More
Defective one- or two-electron reduction of the anticancer anthracycline epirubicin in human heart. Relative importance of vesicular sequestration and impaired efficiency of electron addition.
AuthorsSalvatorelli E, Guarnieri S, Menna P, Liberi G, Calafiore AM, Mariggiò MA, Mordente A, Gianni L, Minotti G
JournalJ Biol Chem
PubMed ID16423826
One-electron quinone reduction and two-electron carbonyl reduction convert the anticancer anthracycline doxorubicin to reactive oxygen species (ROS) or a secondary alcohol metabolite that contributes to inducing a severe form of cardiotoxicity. The closely related analogue epirubicin induces less cardiotoxicity, but the determinants of its different behavior have not been elucidated. ... More
Specific Near-Infrared Probe for Ultrafast Imaging of Lysosomal ß-Galactosidase in Ovarian Cancer Cells.
AuthorsLi X, Pan Y, Chen H, Duan Y, Zhou S, Wu W, Wang S, Liu B
JournalAnal Chem
PubMed ID32212603
'Reactivity based fluorescent probes have been widely investigated as a powerful and noninvasive tool for disease diagnosis in recent years. ß-Galactosidase (ß-gal), one of the typical lysosomal glycosidases, is reported to be a vital biomarker overexpressed in primary ovarian cancer cells. Fluorescent probes with excellent performance for endogenous ß-gal detection ... More
Azithromycin has enhanced effects on lung fibroblasts from idiopathic pulmonary fibrosis (IPF) patients compared to controls [corrected].
AuthorsKrempaska K, Barnowski S, Gavini J, Hobi N, Ebener S, Simillion C, Stokes A, Schliep R, Knudsen L, Geiser TK, Funke-Chambour M
JournalRespir Res
PubMed ID31941499
'Idiopathic pulmonary fibrosis (IPF) is a chronic fatal lung disease without a cure and new drug strategies are urgently needed. Differences in behavior between diseased and healthy cells are well known and drug response can be different between cells isolated from IPF patients and controls. The macrolide Azithromycin (AZT) has ... More
EXOSC10 sculpts the transcriptome during the growth-to-maturation transition in mouse oocytes.
Authors
JournalNucleic Acids Res
PubMed ID32313933
Dstyk mutation leads to congenital scoliosis-like vertebral malformations in zebrafish via dysregulated mTORC1/TFEB pathway.
AuthorsSun X, Zhou Y, Zhang R, Wang Z, Xu M, Zhang D, Huang J, Luo F, Li F, Ni Z, Zhou S, Chen H, Chen S, Chen L, Du X, Chen B, Huang H, Liu P, Yin L, Qiu J, Chen D, Deng C, Xie Y, Luo L, Chen L
JournalNat Commun
PubMed ID31980602
'Congenital scoliosis (CS) is a complex genetic disorder characterized by vertebral malformations. The precise etiology of CS is not fully defined. Here, we identify that mutation in dual serine/threonine and tyrosine protein kinase (dstyk) lead to CS-like vertebral malformations in zebrafish. We demonstrate that the scoliosis in dstyk mutants is ... More
Persistence of a regeneration-associated, transitional alveolar epithelial cell state in pulmonary fibrosis.
Authors
JournalNat Cell Biol
PubMed ID32661339
Oral Nanoparticles Exhibit Specific High-Efficiency Intestinal Uptake and Lymphatic Transport.
Authors
JournalACS Nano
PubMed ID30088412
Multidrug Resistance in Cancer Circumvented Using a Cytosolic Drug Reservoir.
Authors
JournalAdv Sci (Weinh)
PubMed ID29619295
Low-Intensity Focused Ultrasound-Responsive Ferrite-Encapsulated Nanoparticles for Atherosclerotic Plaque Neovascularization Theranostics.
Authors
JournalAdv Sci (Weinh)
PubMed ID34382370
Fluorescent nanodiamond tracking reveals intraneuronal transport abnormalities induced by brain-disease-related genetic risk factors.
Authors
JournalNat Nanotechnol
PubMed ID27893730
β-Coronaviruses Use Lysosomes for Egress Instead of the Biosynthetic Secretory Pathway.
Systematic analysis of ribophagy in human cells reveals bystander flux during selective autophagy.
Authors
JournalNat Cell Biol
PubMed ID29230017
iPSCs from a Hibernator Provide a Platform for Studying Cold Adaptation and Its Potential Medical Applications.
Authors
JournalCell
PubMed ID29576452
Mammalian Atg8 proteins regulate lysosome and autolysosome biogenesis through SNAREs.
AuthorsGu Y, Princely Abudu Y, Kumar S, Bissa B, Choi SW, Jia J, Lazarou M, Eskelinen EL, Johansen T, Deretic V
JournalEMBO J
PubMed ID31625181
Mammalian homologs of yeast Atg8 protein (mAtg8s) are important in autophagy, but their exact mode of action remains ill-defined. Syntaxin 17 (Stx17), a SNARE with major roles in autophagy, was recently shown to bind mAtg8s. Here, we identified LC3-interacting regions (LIRs) in several SNAREs that broaden the landscape of the ... More
Loss of Sirtuin 1 Alters the Secretome of Breast Cancer Cells by Impairing Lysosomal Integrity.
AuthorsLatifkar A, Ling L, Hingorani A, Johansen E, Clement A, Zhang X, Hartman J, Fischbach C, Lin H, Cerione RA, Antonyak MA
JournalDev Cell
PubMed ID30982660
The NAD
Autophagy Regulated by Gain of Function Mutant p53 Enhances Proteasomal Inhibitor-Mediated Cell Death through Induction of ROS and ERK in Lung Cancer Cells.
AuthorsSaini H, Hakeem I, Mukherjee S, Chowdhury S, Chowdhury R
JournalJ Oncol
PubMed ID30723502
Mutations in p53, especially gain of function (GOF) mutations, are highly frequent in lung cancers and are known to facilitate tumor aggressiveness. Yet, the links between mutant GOF-p53 and lung cancers are not well established. In the present study, we set to examine how we can better sensitize resistant GOF-p53 ... More
Magnolol alleviates Alzheimer's disease-like pathology in transgenic C. elegans by promoting microglia phagocytosis and the degradation of beta-amyloid through activation of PPAR-?.
AuthorsXie Z, Zhao J, Wang H, Jiang Y, Yang Q, Fu Y, Zeng H, Hölscher C, Xu J, Zhang Z
JournalBiomed Pharmacother
PubMed ID32000045
This study aims to investigate whether magnolol (MG), a natural neolignane compound, can prevent AD induced by beta-amyloid (Aß) and the possible mechanisms involved. MG dose-dependently reduces Aß deposition, toxicity and memory impairment caused by Aß in transgenic C. elegans. More importantly, these effects are reversed by GW9662, a selective ... More
Hyperglycemia-induced cardiomyocyte death is mediated by lysosomal membrane injury and aberrant expression of cathepsin D.
AuthorsKobayashi S, Zhao F, Kobayashi T, Hagiwara M, Kaminaris A, Li C, Cai F, Huang Y, Liang Q
JournalBiochem Biophys Res Commun
PubMed ID31862139
Hyperglycemia is an independent risk factor for diabetic heart failure. However, the mechanisms that mediate hyperglycemia-induced cardiac damage remain poorly understood. Previous studies have shown an association between lysosomal dysfunction and diabetic heart injury. The present study examined if mimicking hyperglycemia in cultured cardiomyocytes could induce lysosomal membrane permeabilization (LMP), ... More
A Model In Vitro Study Using Hypericin: Tumor-Versus Necrosis-Targeting Property and Possible Mechanisms.
AuthorsLi Y, Wang S, Zhao Y, Saiyin H, He X, Zhao J, Li L, Talebi A, Huang G, Ni Y
JournalBiology (Basel)
PubMed ID31936002
Hypericin (Hyp) had been explored as a tumor-seeking agent for years; however, more recent studies showed its necrosis-avidity rather than cancer-seeking property. To further look into this discrepancy, we conducted an in vitro study on Hyp retention in vital and dead cancerous HepG2 and normal LO2 cell lines by measuring ... More
Effect of novel porphyrazine photosensitizers on normal and tumor brain cells.
AuthorsMishchenko TA, Turubanova VD, Mitroshina EV, Alzeibak R, Peskova NN, Lermontova SA, Klapshina LG, Balalaeva IV, Vedunova MV, Krysko DV
JournalJ Biophotonics
PubMed ID31595675
Photodynamic therapy (PDT) is a clinically approved procedure for targeting tumor cells. Though several different photosensitizers have been developed, there is still much demand for novel photosensitizers with improved properties. In this study we aim to characterize the accumulation, localization and dark cytotoxicity of the novel photosensitizers developed in-house derivatives ... More