'We previously reported the identification of a novel family of immunomodulatory proteins, termed helminth defense molecules (HDMs), that are secreted by medically important trematode parasites. Since HDMs share biochemical, structural, and functional characteristics with mammalian cathelicidin-like host defense peptides (HDPs), we proposed that HDMs modulate the immune response via molecular ... More
Caveolin targeting to late endosome/lysosomal membranes is induced by perturbations of lysosomal pH and cholesterol content.
AuthorsMundy DI, Li WP, Luby-Phelps K, Anderson RG,
JournalMol Biol Cell
PubMed ID22238363
'Caveolin-1 is an integral membrane protein of plasma membrane caveolae. Here we report that caveolin-1 collects at the cytosolic surface of lysosomal membranes when cells are serum starved. This is due to an elevation of the intralysosomal pH, since ionophores and proton pump inhibitors that dissipate the lysosomal pH gradient ... More
Histamine-functionalized copolymer micelles as a drug delivery system in 2D and 3D models of breast cancer.
AuthorsZhang Y, Lundberg P, Diether M, Porsch C, Janson C, Lynd NA, Ducani C, Malkoch M, Malmström E, Hawker CJ, Nyström AM,
Journal
PubMed ID26257912
'Histamine functionalized block copolymers based on poly(allyl glycidyl ether)-b-poly(ethylene oxide) (PAGE-b-PEO) were prepared with different ratios of histamine and octyl or benzyl groups using UV-initiated thiol-ene click chemistry. At neutral pH, the histamine units are uncharged and hydrophobic, while in acidic environments, such as in the endosome, lysosomes, or extracellular ... More
Neuroprotective role of thymoquinone against 1-methyl-4-phenylpyridinium-induced dopaminergic cell death in primary mesencephalic cell culture.
AuthorsRadad KS, Al-Shraim MM, Moustafa MF, Rausch WD,
Journal
PubMed ID25630775
'To investigate potential mechanisms mediating the neuroprotective effect of thymoquinone (TQ) on dopaminergic neurons. This study was conducted in the Chemistry and Biochemistry Institute, University of Veterinary Medicine, Vienna, Austria between June and August 2013. Primary cultures were prepared from embryonic mouse mesencephala (OFI/SPF) at gestation day 14. Four sets ... More
Therapeutic efficacy of FTY720 in a rat model of NK-cell leukemia.
AuthorsLiao A, Broeg K, Fox T, Tan SF, Watters R, Shah MV, Zhang LQ, Li Y, Ryland L, Yang J, Aliaga C, Dewey A, Rogers A, Loughran K, Hirsch L, Jarbadan NR, Baab KT, Liao J, Wang HG, Kester M, Desai D, Amin S, Loughran TP, Liu X,
JournalBlood
PubMed ID21768294
'NK-cell leukemia is a clonal expansion of NK cells. The illness can occur in an aggressive or chronic form. We studied cell lines from human and rat NK-cell leukemias (aggressive NK-cell leukemia) as well as samples from patients with chronic NK-cell leukemia to investigate pathogenic mechanisms. Here we report that ... More
Effects of chlorin e6-mediated photodynamic therapy on human colon cancer SW480 cells.
AuthorsLi Y, Yu Y, Kang L, Lu Y,
Journal
PubMed ID25663983
'This study is to investigate the antitumor effects and possible mechanisms of chlorin e6-mediated photodynamic therapy (Ce6-PDT) on human colon cancer SW480 cells. SW480 cells were treated with Ce6, followed by photodynamic irradiation. Subcellular localization of Ce6 in SW480 cells was observed with confocal laser scanning microscopy (LSCM). Reactive oxygen ... More
Degradable ketal-based block copolymer nanoparticles for anticancer drug delivery: a systematic evaluation.
AuthorsLouage B, Zhang Q, Vanparijs N, Voorhaar L, Vande Casteele S, Shi Y, Hennink WE, Van Bocxlaer J, Hoogenboom R, De Geest BG,
Journal
PubMed ID25490543
'Low solubility of potent (anticancer) drugs is a major driving force for the development of noncytotoxic, stimuli-responsive nanocarriers, including systems based on amphiphilic block copolymers. In this regard, we investigated the potential of block copolymers based on 2-hydroxyethyl acrylate (HEA) and the acid-sensitive ketal-containing monomer (2,2-dimethyl-1,3-dioxolane-4-yl)methyl acrylate (DMDMA) to form ... More
ß2-microglobulin amyloid fibrils are nanoparticles that disrupt lysosomal membrane protein trafficking and inhibit protein degradation by lysosomes.
AuthorsJakhria T, Hellewell AL, Porter MY, Jackson MP, Tipping KW, Xue WF, Radford SE, Hewitt EW,
Journal
PubMed ID25378395
'Fragmentation of amyloid fibrils produces fibrils that are reduced in length but have an otherwise unchanged molecular architecture. The resultant nanoscale fibril particles inhibit the cellular reduction of the tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), a substrate commonly used to measure cell viability, to a greater extent than unfragmented fibrils. Here ... More
pH-responsive biocompatible fluorescent polymer nanoparticles based on phenylboronic acid for intracellular imaging and drug delivery.
AuthorsLi S, Hu K, Cao W, Sun Y, Sheng W, Li F, Wu Y, Liang XJ,
Journal
PubMed ID25278283
'To address current medical challenges, there is an urgent need to develop drug delivery systems with multiple functions, such as simultaneous stimuli-responsive drug release and real-time imaging. Biocompatible polymers have great potential for constructing smart multifunctional drug-delivery systems through grafting with other functional ligands. More importantly, novel biocompatible polymers with ... More
Nanoconjugation: A Materials Approach to Enhance Epidermal Growth Factor Induced Apoptosis.
AuthorsWu L, Yu X, Feizpour A, Reinhard BM,
Journal
PubMed ID24683470
'Apoptosis evasion is a hallmark of cancer that motivates the development of novel strategies for inducing cell death in a controlled fashion. The size-compatibility of nanoparticles (NPs) with cellular components provides new opportunities for regulating cellular processes, potentially including apoptosis. We investigated the impact of the covalent attachment of epidermal ... More
A phosphorescent rhenium(I) histone deacetylase inhibitor: mitochondrial targeting and paraptosis induction.
AuthorsYe RR, Tan CP, Lin YN, Ji LN, Mao ZW,
Journal
PubMed ID25882790
In this report, we designed a histone deacetylase-targeted phosphorescent Re(I) complex ReLMito. Colocalization studies suggested that ReLMito could specially localize to mitochondria. We also demonstrated that ReLMito could induce paraptosis in cancer cells. These features endowed the complex with potential to induce and monitor mitochondrial morphological changes during the paraptosis ... More
Multifunctional self-assembled polymeric nanoprobes for FRET-based ratiometric detection of mitochondrial H2O2 in living cells.
AuthorsQiao J, Liu Z, Tian Y, Wu M, Niu Z,
Journal
PubMed ID25642908
A ratiometric, multifunctional nanoprobe was prepared consisting of a self-assembled polymeric micelle as the carrier, tetraphenylethene (TPE) as the donor, fluorescent boronate as the H2O2-responsive acceptor, and triphenylphosphonium as a mitochondria-targeted moiety. The assembled nanoparticles could detect both exogenous and endogenous mitochondrial H2O2 changes in living cells. ... More
Mitochondrially targeted redox probe reveals the variations in oxidative capacity of the haematopoietic cells.
AuthorsKaur A, Brigden KW, Cashman TF, Fraser ST, New EJ,
Journal
PubMed ID26006184
Both oxidative stress and mitochondrial dysfunction play roles in a myriad of pathological conditions. There is therefore a need for tools that possess the ability to measure the dynamics of oxidative capacity within the mitochondria, particularly those that can measure reversible changes. Here, we report a mitochondrially-targeted fluorescent redox sensor ... More
Mitochondria-targeted ratiometric fluorescent probe for real time monitoring of pH in living cells.
AuthorsWu MY, Li K, Liu YH, Yu KK, Xie YM, Zhou XD, Yu XQ,
Journal
PubMed ID25890762
Pyridinium functioned 7-hydroxy coumarin was presented as the first mitochondria-targeted ratiometric fluorescent probe CP for real time monitoring pH in living cells. Compared with commercially available mitochondrial trackers, CP possesses high specificity to mitochondria in living cells as well as good biocompatibility. Meanwhile, CP displays excellent pH sensitivity and anti-interference ... More
pH-responsive PDMS-b-PDMAEMA micelles for intracellular anticancer drug delivery.
AuthorsCar A, Baumann P, Duskey JT, Chami M, Bruns N, Meier W,
Journal
PubMed ID25068477
A series of poly(dimethysiloxane)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMS-b-PDMAEMA) block copolymers were synthesized with atom transfer radical polymerization (ATRP). In aqueous solution the polymers self-assembled into micelles with diameters between 80 and 300 nm, with the ability to encapsulate DOX. The polymer with the shortest PDMAEMA block (5 units) displayed excellent cell viability, ... More
HIV-1 Tat protein induces glial cell autophagy through enhancement of BAG3 protein levels.
AuthorsBruno AP, De Simone FI, Iorio V, De Marco M, Khalili K, Sariyer IK, Capunzo M, Nori SL, Rosati A,
Journal
PubMed ID25483098
BAG3 protein has been described as an anti-apoptotic and pro-autophagic factor in several neoplastic and normal cells. We previously demonstrated that BAG3 expression is elevated upon HIV-1 infection of glial and T lymphocyte cells. Among HIV-1 proteins, Tat is highly involved in regulating host cell response to viral infection. Therefore, ... More
Gastrokine-2 is transiently expressed in the endodermal and endothelial cells of the maturing mouse yolk sac.
The yolk sac (YS) is a thin, bi-layered membrane encompassing the developing mammalian embryo in utero. The outer layer of the YS is composed of visceral endodermal cells derived from the primitive endoderm. The inner mesenchymal layer is highly vascularised and the first source of haematopoietic cells. YS haematopoiesis takes ... More
Lysosomal drug sequestration as a mechanism of drug resistance in vascular sarcoma cells marked by high CSF-1R expression.
AuthorsGorden BH, Saha J, Khammanivong A, Schwartz GK, Dickerson EB,
Journal
PubMed ID25295160
Human angiosarcoma and canine hemangiosarcoma are thought to arise from vascular tissue or vascular forming cells based upon their histological appearance. However, recent evidence indicates a hematopoietic or angioblastic cell of origin for these tumors. In support of this idea, we previously identified an endothelial-myeloid progenitor cell population with high ... More
A small molecule restores function to TRPML1 mutant isoforms responsible for mucolipidosis type IV.
AuthorsChen CC, Keller M, Hess M, Schiffmann R, Urban N, Wolfgardt A, Schaefer M, Bracher F, Biel M, Wahl-Schott C, Grimm C,
Journal
PubMed ID25119295
Mucolipidosis type IV (MLIV) is an autosomal recessive lysosomal storage disorder often characterized by severe neurodevelopmental abnormalities and neuro-retinal degeneration. Mutations in the TRPML1 gene are causative for MLIV. We used lead optimization strategies to identify--and MLIV patient fibroblasts to test--small-molecule activators for their potential to restore TRPML1 mutant channel ... More
Drosophila acinus encodes a novel regulator of endocytic and autophagic trafficking.
AuthorsHaberman AS, Akbar MA, Ray S, Krämer H,
JournalDevelopment
PubMed ID20504956
Endosomal trafficking affects many cellular pathways from cell signaling to metabolism, but little is known about how these effects are coordinated. In a genetic screen for mutants affecting endosomal trafficking, we identified Drosophila acinus (dacn; hook-like). Its mammalian homolog Acinus has been implicated in RNA processing and chromatin fragmentation during ... More
Scavenger receptor-recognized and enzyme-responsive nanoprobe for fluorescent labeling of lysosomes in live cells.
AuthorsFan Y, Li F, Chen D,
Journal
PubMed ID24929616
Lysosomal imaging represents a potent tool for investigating the organization of related cellular events and their modulation via diagnostic and therapeutic approaches. However, specific labeling of the lysosome in live cells is a significant challenge. Taking advantage of the inherent lysosomal entry of nanoparticles and unique digestive inclusions in the ... More
Central role of mitofusin 2 in autophagosome-lysosome fusion in cardiomyocytes.
AuthorsZhao T, Huang X, Han L, Wang X, Cheng H, Zhao Y, Chen Q, Chen J, Cheng H, Xiao R, Zheng M,
JournalJ Biol Chem
PubMed ID22619176
In the heart, autophagy has been implicated in cardioprotection and ischemia-reperfusion tolerance, and the dysregulation of autophagy is associated with the development of heart failure. Mitochondrial dynamic proteins are profoundly involved in autophagic processes, especially the initiation and formation of autophagosomes, but it is not clear whether they play any ... More
Tools and techniques to measure mitophagy using fluorescence microscopy.
AuthorsDolman NJ, Chambers KM, Mandavilli B, Batchelor RH, Janes MS,
Journal
PubMed ID24121704
Mitophagy is a specialized form of autophagy that removes damaged mitochondria, thereby maintaining efficient cellular metabolism and reducing cellular stress caused by aberrant oxidative bursts. Deficits in mitophagy underlie several diseases, and a substantial body of research has elucidated key steps in the pathways that lead to and execute autophagic ... More
Global Landscape and Dynamics of Parkin and USP30-Dependent Ubiquitylomes in iNeurons during Mitophagic Signaling.
Authors
JournalMol Cell
PubMed ID32142685
Phase separation of Nur77 mediates celastrol-induced mitophagy by promoting the liquidity of p62/SQSTM1 condensates.
Authors
JournalNat Commun
PubMed ID34645818
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
mTORC1 Activation Requires DRAM-1 by Facilitating Lysosomal Amino Acid Efflux.
Authors
JournalMol Cell
PubMed ID31492633
Identification of Required Host Factors for SARS-CoV-2 Infection in Human Cells.
Authors
JournalCell
PubMed ID33147445
Ejection of damaged mitochondria and their removal by macrophages ensure efficient thermogenesis in brown adipose tissue.
Authors
JournalCell Metab
PubMed ID35305295
Altered function and differentiation of age-associated B cells contribute to the female bias in lupus mice.
Authors
JournalNat Commun
PubMed ID34376664
Therapeutic efficacy of antisense oligonucleotides in mouse models of CLN3 Batten disease.
Authors
JournalNat Med
PubMed ID32719489
Salinomycin kills cancer stem cells by sequestering iron in lysosomes.
Authors
JournalNat Chem
PubMed ID28937680
Minimal genetically encoded tags for fluorescent protein labeling in living neurons.
Authors
JournalNat Commun
PubMed ID35031604
DNA damage invokes mitophagy through a pathway involving Spata18.
Authors
JournalNucleic Acids Res
PubMed ID32453416
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