A genetic screen in zebrafish identifies the mutants vps18, nf2 and foie gras as models of liver disease.
AuthorsSadler KC, Amsterdam A, Soroka C, Boyer J, Hopkins N
JournalDevelopment
PubMed ID16000385
'Hepatomegaly is a sign of many liver disorders. To identify zebrafish mutants to serve as models for hepatic pathologies, we screened for hepatomegaly at day 5 of embryogenesis in 297 zebrafish lines bearing mutations in genes that are essential for embryonic development. Seven mutants were identified, and three have phenotypes ... More
PLA2 activity is required for nuclear shrinkage in caspase-independent cell death.
AuthorsShinzawa K, Tsujimoto Y
JournalJ Cell Biol
PubMed ID14676306
'Apoptosis is defined on the basis of morphological changes like nuclear fragmentation and chromatin condensation, which are dependent on caspases. Many forms of caspase-independent cell death have been reported, but the mechanisms are still poorly understood. We found that hypoxic cell death was independent of caspases and was associated with ... More
Identification of superoxide dismutase as a cofactor for the pseudomonas type III toxin, ExoU.
AuthorsSato H, Feix JB, Frank DW
JournalBiochemistry
PubMed ID16922513
'Pseudomonas aeruginosa is an opportunistic pathogen that uses a type III secretion system and four effector proteins to avoid innate immune responses. ExoS, ExoT, ExoY, and ExoU all possess enzymatic activities that disrupt host cellular physiology and prevent bacterial clearance by host defense mechanisms. The specificity of these toxins for ... More
Vascular lipid accumulation, lipoprotein oxidation, and macrophage lipid uptake in hypercholesterolemic zebrafish.
AuthorsStoletov K, Fang L, Choi SH, Hartvigsen K, Hansen LF, Hall C, Pattison J, Juliano J, Miller ER, Almazan F, Crosier P, Witztum JL, Klemke RL, Miller YI,
JournalCirc Res
PubMed ID19265037
'Lipid accumulation in arteries induces vascular inflammation and atherosclerosis, the major cause of heart attack and stroke in humans. Extreme hyperlipidemia induced in mice and rabbits enables modeling many aspects of human atherosclerosis, but microscopic examination of plaques is possible only postmortem. Here we report that feeding adult zebrafish (Danio ... More
Group V phospholipase A2 induces leukotriene biosynthesis in human neutrophils through the activation of group IVA phospholipase A2.
AuthorsKim YJ, Kim KP, Han SK, Munoz NM, Zhu X, Sano H, Leff AR, Cho W
JournalJ Biol Chem
PubMed ID12124392
'We reported previously that exogenously added human group V phospholipase A(2) (hVPLA(2)) could elicit leukotriene B(4) (LTB(4)) biosynthesis in human neutrophils (Han, S. K., Kim, K. P., Koduri, R., Bittova, L., Munoz, N. M., Leff, A. R., Wilton, D. C., Gelb, M. H., and Cho, W. (1999) J. Biol. Chem. ... More
Phosphatidylcholine homeostasis and liver failure.
AuthorsLi Z, Agellon LB, Vance DE
JournalJ Biol Chem
PubMed ID16144842
'In mammals, the only endogenous pathway for choline biosynthesis is the methylation of phosphatidylethanolamine to phosphatidylcholine (PC) by phosphatidylethanolamine N-methyltransferase (PEMT) coupled to PC degradation. Complete choline deprivation in mice by feeding Pemt(-/-) mice a choline-deficient (CD) diet decreases hepatic PC by 50% and is lethal within 5 days. PC ... More
A sensitive fluorescence-based assay for the detection of ExoU-mediated PLA(2) activity.
AuthorsBenson MA, Schmalzer KM, Frank DW,
JournalClin Chim Acta
PubMed ID19900431
'BACKGROUND: Pseudomonas aeruginosa is an opportunistic pathogen that causes disease in immunocompromised individuals, burn victims, and cystic fibrosis patients. Strains that secrete ExoU induce host cell lysis and damage epithelial tissue, which can lead to severe outcomes including sepsis and mortality. ExoU is classified as an A2 phospholipase (PLA(2)) and ... More
Interaction of low molecular weight group IIA phospholipase A2 with apoptotic human T cells: role of heparan sulfate proteoglycans.
AuthorsBoilard E, Bourgoin SG, Bernatchez C, Poubelle PE, Surette ME
JournalFASEB J
PubMed ID12773489
'Human group IIA phospholipase A2 (hIIA PLA2) is a 14 kDa secreted enzyme associated with inflammatory diseases. A newly discovered property of hIIA PLA2 is the binding affinity for the heparan sulfate proteoglycan (HSPG) glypican-1. In this study, the binding of hIIA PLA2 to apoptotic human T cells was investigated. ... More
Essential role of p38 MAPK in caspase-independent, iPLA(2)-dependent cell death under hypoxia/low glucose conditions.
AuthorsAoto M, Shinzawa K, Suzuki Y, Ohkubo N, Mitsuda N, Tsujimoto Y,
JournalFEBS Lett
PubMed ID19393651
'The mechanisms of cell death induced by hypoxia or ischemia are not yet fully understood. We have previously demonstrated that cell death induced by hypoxia occurs independently of caspases, and is mediated by phospholipase A(2) (PLA(2)). Here, we show that p38 mitogen-activated protein kinase is activated under hypoxia. A selective ... More
Genetic analysis of digestive physiology using fluorescent phospholipid reporters.
AuthorsFarber SA, Pack M, Ho SY, Johnson ID, Wagner DS, Dosch R, Mullins MC, Hendrickson HS, Hendrickson EK, Halpern ME
JournalScience
PubMed ID11359013
'Zebrafish are a valuable model for mammalian lipid metabolism; larvae process lipids similarly through the intestine and hepatobiliary system and respond to drugs that block cholesterol synthesis in humans. After ingestion of fluorescently quenched phospholipids, endogenous lipase activity and rapid transport of cleavage products results in intense gall bladder fluorescence. ... More
Real-time cell assays of phospholipase A(2)s using fluorogenic phospholipids.
AuthorsManna D, Cho W,
JournalMethods Enzymol
PubMed ID17954240
'Phospholipase A(2)s (PLA(2)s) are a superfamily of enzymes involved in production of a wide variety of lipid mediators, including arachidonic acid, lysophospholipids, platelet activation factor, and eicosanoids. Fluorescence-based, real-time cellular activity assays for PLA(2)s have been developed as a tool for studying the function and spatiotemporal regulation of PLA(2)s. Recent ... More
A novel fluorogenic substrate for the measurement of endothelial lipase activity.
'Endothelial lipase (EL) is a phospholipase A1 (PLA1) enzyme that hydrolyzes phospholipids at the sn-1 position to produce lysophospholipids and free fatty acids. Measurement of the PLA1 activity of EL is usually accomplished by the use of substrates that are also hydrolyzed by lipases in other subfamilies such as PLA2 ... More
Cytosolic phospholipase A2-{alpha} is an early apoptotic activator in PEDF-induced endothelial cell apoptosis.
AuthorsHo TC, Chen SL, Yang YC, Lo TH, Hsieh JW, Cheng HC, Tsao YP,
JournalAm J Physiol Cell Physiol
PubMed ID19091957
'Pigment epithelium-derived factor (PEDF) is an intrinsic antiangiogenic factor and a potential therapeutic agent. Previously, we discovered the mechanism of PEDF-induced apoptosis of human umbilical vein endothelial cells (HUVECs) as sequential induction/activation of p38 mitogen-activated protein kinase (MAPK), peroxisome proliferator-activated receptor gamma (PPAR-gamma), and p53. In the present study, we ... More
Zebrafish earns its stripes in genetic screens.
AuthorsVogel G
JournalScience
PubMed ID10841731
Activation of a bacterial virulence protein by the GTPase RhoA.
AuthorsChristen M, Coye LH, Hontz JS, LaRock DL, Pfuetzner RA, Megha, Miller SI,
JournalSci Signal
PubMed ID19887681
The Rho family of guanosine triphosphatases (GTPases) are essential eukaryotic signaling molecules that regulate cellular physiology. Virulence factors from various pathogens alter the signaling of GTPases by acting as GTPase activating factors, guanine nucleotide exchange factors, or direct covalent modifiers; however, bacterial virulence factors that sense rather than alter the ... More
A high-throughput screen for endothelial lipase using HDL as substrate.
AuthorsKeller PM, Rust T, Murphy DJ, Matico R, Trill JJ, Krawiec JA, Jurewicz A, Jaye M, Harpel M, Thrall S, Schwartz B,
JournalJ Biomol Screen
PubMed ID18566479
Endothelial lipase (EL) is a 482-amino-acid protein from the triglyceride lipase gene family that uses a Ser-His-Asp triad for catalysis. Its expression in endothelial cells and preference for phospholipids rather than triglycerides are unique. Animal models in which it is overexpressed or knocked out indicate EL levels are inversely correlated ... More
Systematic evaluation of transcellular activities of secretory phospholipases A2. High activity of group V phospholipases A2 to induce eicosanoid biosynthesis in neighboring inflammatory cells.
AuthorsWijewickrama GT, Kim JH, Kim YJ, Abraham A, Oh Y, Ananthanarayanan B, Kwatia M, Ackerman SJ, Cho W
JournalJ Biol Chem
PubMed ID16476735
The mechanisms by which secretory phospholipase A2 (PLA2) exerts cellular effects are not fully understood. To elucidate these mechanisms, we systematically and quantitatively assessed the activities of human group IIA, V, and X PLA2s on originating and neighboring cells using orthogonal fluorogenic substrates in various mixed cell systems. When HEK293 ... More
Distinct signals from the microbiota promote different aspects of zebrafish gut differentiation.
AuthorsBates JM, Mittge E, Kuhlman J, Baden KN, Cheesman SE, Guillemin K
JournalDev Biol
PubMed ID16781702
All animals exist in intimate associations with microorganisms that play important roles in the hosts' normal development and tissue physiology. In vertebrates, the most populous and complex community of microbes resides in the digestive tract. Here, we describe the establishment of the gut microbiota and its role in digestive tract ... More
Intramolecularly quenched BODIPY-labeled phospholipid analogs in phospholipase A(2) and platelet-activating factor acetylhydrolase assays and in vivo fluorescence imaging.
AuthorsHendrickson HS, Hendrickson EK, Johnson ID, Farber SA
JournalAnal Biochem
PubMed ID10585741
Phospholipase substrate analogs containing both a fluorescent BODIPY group and a quenching 2,4-dinitrophenyl (DNP) group were synthesized. They showed little fluorescence, but upon hydrolysis became fluorescent as the quenching group was removed. Two substrates were phosphatidylethanolamine analogs with a BODIPY-pentanoyl group at the sn-2 position and DNP linked to the ... More
Identification of an autoantigen on the surface of apoptotic human T cells as a new protein interacting with inflammatory group IIA phospholipase A2.
AuthorsBoilard E, Bourgoin SG, Bernatchez C, Surette ME
JournalBlood
PubMed ID12829607
One of the most studied secreted phospholipases A2 (sPLA2), the group IIA sPLA2, is found at high levels in inflammatory fluids of patients with autoimmune diseases. A characteristic of group IIA sPLA2 is its preference for negatively charged phospholipids, which become exposed on the extracellular leaflet of apoptotic cell membranes. ... More
Fluorometric assays of phospholipase A2 activity with three different substrates in biological samples of patients with schizophrenia.
AuthorsLasch J, Willhardt I, Kinder D, Sauer H, Smesny S
JournalClin Chem Lab Med
PubMed ID12940517
The rationale of this study was to understand the complexity of kinetics of fluorogenic phospholipid substrates as well as contradictory findings of clinical papers measuring phospholipase A2 (PLA2) activity using different methodologies. The aim was to recommend to clinicians and researchers what substrate in conjunction with what assay should be ... More
Microsomal triglyceride transfer protein is required for yolk lipid utilization and absorption of dietary lipids in zebrafish larvae.
AuthorsSchlegel A, Stainier DY
JournalBiochemistry
PubMed ID17176039
Although the absorption, transport, and catabolism of dietary lipids have been studied extensively in great detail in mammals and other vertebrates, a tractable genetic system for identifying novel genes involved in these physiologic processes is not available. To establish such a model, we monitored neutral lipid by staining fixed zebrafish ... More
Human group V phospholipase A2 induces group IVA phospholipase A2-independent cysteinyl leukotriene synthesis in human eosinophils.
AuthorsMuñoz NM, Kim YJ, Meliton AY, Kim KP, Han SK, Boetticher E, O'Leary E, Myou S, Zhu X, Bonventre JV, Leff AR, Cho W
JournalJ Biol Chem
PubMed ID12796497
We previously reported that exogenously added human group V phospholipase A2 (hVPLA2) could elicit leukotriene B4 biosynthesis in human neutrophils through the activation of group IVA phospholipase A2 (cPLA2) (Kim, Y. J., Kim, K. P., Han, S. K., Munoz, N. M., Zhu, X., Sano, H., Leff, A. R., and Cho, ... More
Heterotrimeric G-proteins Activate Cl- Channels through Stimulation of a Cyclooxygenase-dependent Pathway in a Model Liver Cell Line.
Authors Kilic Gordan; Fitz J Gregory;
JournalJ Biol Chem
PubMed ID11812774
Circulating hormones produce rapid changes in the Cl(-) permeability of liver cells through activation of plasma membrane receptors coupled to heterotrimeric G-proteins. The resulting effects on intracellular pH, membrane potential, and Cl(-) content are important contributors to the overall metabolic response. Consequently, the purpose of these studies was to evaluate ... More
Discovery of a NAPE-PLD inhibitor that modulates emotional behavior in mice.
Authors
JournalNat Chem Biol
PubMed ID32393901
In vivo imaging of zebrafish digestive organ function using multiple quenched fluorescent reporters.
Authors
JournalAm J Physiol Gastrointest Liver Physiol
PubMed ID19056761
Defining hepatic dysfunction parameters in two models of fatty liver disease in zebrafish larvae.
Authors
JournalZebrafish
PubMed ID23697887
Structure-Activity Relationship Studies of Pyrimidine-4-Carboxamides as Inhibitors of N-Acylphosphatidylethanolamine Phospholipase D.
Authors
JournalJ Med Chem
PubMed ID33382264
Deficiency in class III PI3-kinase confers postnatal lethality with IBD-like features in zebrafish.
Authors
JournalNat Commun
PubMed ID29980668
cAMP signaling primes lung endothelial cells to activate caspase-1 during Pseudomonas aeruginosa infection.