scholarly journals Incorporation of serine into Paramecium ethanolamine phospholipid and phosphonolipid head groups

1984 ◽  
Vol 222 (1) ◽  
pp. 229-233 ◽  
Author(s):  
D F Matesic ◽  
E S Kaneshiro
Keyword(s):  
De Novo ◽  
Cell Types ◽  
Head Groups ◽  
Ethanolamine Phospholipid

Ethanolamine phospholipid head groups in Paramecium were synthesized directly from ethanolamine. As in other cell types, radioactivity from ethanolamine failed to incorporate significantly into head groups of ethanolamine phosphonolipids, indicating that the phosphonolipids are not derived from their phospholipid analogues. Unlike other systems previously examined, radioactivity from serine is incorporated into both ethanolamine phospholipid and phosphonolipid head groups of glycerolipids and sphingolipids in this ciliate. These observations suggest that synthesis of ethanolamine phosphonolipids involves synthesis de novo of free phosphonoserine, which is then incorporated into lipids, and then lipid-bound phosphonoserine intermediates (glycerolipids or sphingolipids) undergo decarboxylation, forming lipidbound phosphonoethanolamine compounds.

Antileukemic activity of rapamycin in acute myeloid leukemia

Blood ◽  
2005 ◽  
Vol 105 (6) ◽  
pp. 2527-2534 ◽  
Author(s):  
Christian Récher ◽  
Odile Beyne-Rauzy ◽  
Cécile Demur ◽  
Gaëtan Chicanne ◽  
Cédric Dos Santos ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Mammalian Target Of Rapamycin ◽  
Cell Types ◽  
Mtor Inhibition ◽  
Growth And Survival ◽  
Clinical Responses ◽  
De Novo Aml ◽  
Acute Myeloid

AbstractThe mammalian target of rapamycin (mTOR) is a key regulator of growth and survival in many cell types. Its constitutive activation has been involved in the pathogenesis of various cancers. In this study, we show that mTOR inhibition by rapamycin strongly inhibits the growth of the most immature acute myeloid leukemia (AML) cell lines through blockade in G0/G1 phase of the cell cycle. Accordingly, 2 downstream effectors of mTOR, 4E-BP1 and p70S6K, are phosphorylated in a rapamycin-sensitive manner in a series of 23 AML cases. Interestingly, the mTOR inhibitor markedly impairs the clonogenic properties of fresh AML cells while sparing normal hematopoietic progenitors. Moreover, rapamycin induces significant clinical responses in 4 of 9 patients with either refractory/relapsed de novo AML or secondary AML. Overall, our data strongly suggest that mTOR is aberrantly regulated in most AML cells and that rapamycin and analogs, by targeting the clonogenic compartment of the leukemic clone, may be used as new compounds in AML therapy.

Insulin-Sensitive Phospholipid Signaling Systems and Glucose Transport. Update II

2001 ◽  
Vol 226 (4) ◽  
pp. 283-295 ◽  
Author(s):  
Robert V. Farese
Keyword(s):  
Protein Kinase ◽  
Glucose Metabolism ◽  
Glucose Transport ◽  
Intracellular Signaling ◽  
Glucose Transporter ◽  
De Novo ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Cell Types ◽  
Biologically Active

Insulin provokes rapid changes in phospholipid metabolism and thereby generates biologically active lipids that serve as intracellular signaling factors that regulate glucose transport and glycogen synthesis. These changes include: (i) activation of phosphatidylinositol 3-kinase (PI3K) and production of PIP3; (ii) PIP3-dependent activation of atypical protein kinase Cs (PKCs); (iii) PIP3-dependent activation of PKB; (iv) PI3K-dependent activation of phospholipase D and hydrolysis of phosphatidyicholine with subsequent increases in phosphatidic acid (PA) and diacyiglycerol (DAG); (v) PI3K-independent activation of glycerol-3-phosphate acylytansferase and increases in de novo synthesis of PA and DAG; and (vi) activation of DAG-sensitive PKCs. Recent findings suggest that atypical PKCs and PKB serve as important positive regulators of insulin-stimulated glucose metabolism, whereas mechanisms that result in the activation of DAG-sensitive PKCs serve mainly as negative regulators of insulin signaling through PI3K. Atypical PKCs and PKB are rapidly activated by insulin in adipocytes, liver, skeletal muscles, and other cell types by a mechanism requiring PI3K and its downstream effector, 3-phosphoinositide-dependent protein kinase-1 (PDK-1), which, in conjunction with PIP3, phosphorylates critical threonine residues in the activation loops of atypical PKCs and PKB. PIP3 also promotes increases in autophosphorylation and allosteric activation of atypical PKCs. Atypical PKCs and perhaps PKB appear to be required for insulin-induced translocation of the GLUT 4 glucose transporter to the plasma membrane and subsequent glucose transport. PKB also appears to be the major regulator of glycogen synthase. Together, atypical PKCs and PKB serve as a potent, integrated PI3K/PDK-1-directed signaling system that is used by insulin to regulate glucose metabolism.

scholarly journals Epithelial argininosuccinate synthetase is dispensable for intestinal regeneration and tumorigenesis

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Jonathan H. M. van der Meer ◽  
Ruben J. de Boer ◽  
Bartolomeus J. Meijer ◽  
Wouter L. Smit ◽  
Jacqueline L. M. Vermeulen ◽  
...  
Keyword(s):  
Amino Acid ◽  
Intestinal Epithelium ◽  
De Novo ◽  
Cell Types ◽  
Intestinal Epithelial ◽  
Argininosuccinate Synthetase ◽  
Important Amino Acid ◽  
Tissue Specimens ◽  
Colorectal Cancer Patients

AbstractThe epithelial signaling pathways involved in damage and regeneration, and neoplastic transformation are known to be similar. We noted upregulation of argininosuccinate synthetase (ASS1) in hyperproliferative intestinal epithelium. Since ASS1 leads to de novo synthesis of arginine, an important amino acid for the growth of intestinal epithelial cells, its upregulation can contribute to epithelial proliferation necessary to be sustained during oncogenic transformation and regeneration. Here we investigated the function of ASS1 in the gut epithelium during tissue regeneration and tumorigenesis, using intestinal epithelial conditional Ass1 knockout mice and organoids, and tissue specimens from colorectal cancer patients. We demonstrate that ASS1 is strongly expressed in the regenerating and Apc-mutated intestinal epithelium. Furthermore, we observe an arrest in amino acid flux of the urea cycle, which leads to an accumulation of intracellular arginine. However, loss of epithelial Ass1 does not lead to a reduction in proliferation or increase in apoptosis in vivo, also in mice fed an arginine-free diet. Epithelial loss of Ass1 seems to be compensated by altered arginine metabolism in other cell types and the liver.

Fluorescent phospholipids preferentially accumulate in sub-tegumental cells of schistosomula of Schistosoma mansoni

1992 ◽  
Vol 103 (3) ◽  
pp. 823-830 ◽  
Author(s):  
S.T. Furlong ◽  
K.S. Thibault ◽  
R.A. Rogers
Keyword(s):  
Cellular Network ◽  
Biochemical Analysis ◽  
Phosphatidyl Ethanolamine ◽  
De Novo ◽  
Cell Types ◽  
Host Immunity ◽  
Epifluorescence Microscopy ◽  
Specific Cell ◽  
Back Exchange ◽  
Intact Molecule

Schistosomes do not make sterols or fatty acids de novo and thus require host lipids for survival. The acquisition of host lipids may also be an important factor in the schistosome's defense from host immunity; however, little is known about the regulation of this process. Here we have examined binding of radiolabeled and fluorescently labeled liposomes to schistosomula, and followed incorporation of fluorescent phospholipids into the worm by both morphological and biochemical methods. Saturable binding of radiolabeled phosphatidylcholine containing liposomes was observed and epifluorescence microscopy showed binding of C6-NBD-phosphatidylcholine (C6-NBD-PC), C12-NBD-phosphatidylcholine (C12-NBD-PC) and C6-NBD-phosphatidyl-ethanolamine (C6-NBD-PE) containing liposomes on the surface of the parasite. Following back-exchange with unlabeled liposomes, NBD-PC and NBD-PE were observed to be preferentially incorporated into specific cell types within the worm. Furthermore, cells which had accumulated the fluorescent lipid formed an interconnecting cellular network immediately below the tegument, identified as cytons. By contrast, fluorescein-PE was found only on the surface of the parasite and in the gut but not in the cytons. Biochemical analysis demonstrated that > 90% of the C6-NBD-PC and C12-NBD-PC remained as the intact molecule after a one hour incubation with the parasite, but that greater than 70% of the NBD-PE was converted to other lipids. These studies demonstrate that incorporation of phospholipid analogs into schistosomula can be followed morphologically and biochemically. As there was little localization of NBD-PE or NBD-PC in the gut, these analogs must be assimilated by crossing the tegument.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract 897: Alliance of Blood Derived Endothelial Cells and Adipose Stromal Cells in Human Vasculogenesis

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Dmitry O Traktuev ◽  
Daniel N Prater ◽  
Aravind R Sanjeevaiah ◽  
Stephanie Merfeld-Clauss ◽  
Brian H Johnstone ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Stromal Cells ◽  
De Novo ◽  
Functional Integration ◽  
Cell Types ◽  
Specific Marker ◽  
Pronounced Difference ◽  
Adipose Stromal Cells ◽  
Small Vessels

Introduction Both Endothelial progenitor cells (EPC) and adipose stromal cells (ASC) are under investigation as therapies for cardiovascular diseases. Both cell types are capable of modulating vascular assembly and are, thereby, capable of directly promoting revascularization of ischemic tissues. We have shown that EPC differentiate into endothelial cells to form small vessels, whereas ASC have pericytic properties and naturally stabilize vessels. In this study we tested the possibility that ASC would interact with EPC to assemble de novo vessels in collagen in an in vivo chimeric implant. Methods and Results Collagen implants embedded with either umbilical cord blood EPC or adult ASC or a 4:1 mixture of both (2x10 6 cells/ml) were implanted subcutaneously into NOD/SCID mice. After 14 d implants were harvested and evaluated by immunohistochemistry. There was a pronounced difference among the groups in vascular network assembly. The majority of vessels formed in the EPC and ASC monocultures were small capillaries bounded by a single endothelial layer. Conversely, 100% of the plugs embedded with both cell types were highly invaded with multilayered arteriolar vessels. The density of the CD31 + vessels in the EPC and co-culture plugs was 26.6 ± 5.8 and 122.4 ± 9.8 per mm 2 , respectively. No CD31 + cells of human origin were detected in the ASC monocultures, indicating that ASC, which do not express this EC-specific marker, engage murine EC or form pseudovessels in this system. The density of α-SMA + vessels with lumens per mm 2 was 13.1 ± 3.6 (EPC), 10.2 ± 3.5 (ASC) and 124.7 ± 19.7 (co-culture). The total overlap of CD31 + and SMA + vessels demonstrates that mature, multilayered conduits were formed with the co-culture. Moreover, the majority of these vessels were filled with erythrocytes (92.5 ± 16.2 per mm 2 ), indicating inosculation with the native vasculature, which was confirmed by ultrasound with echogenic microbubbles and persisted to at least 4 months. Conclusion This study is the first to demonstrate that non-transformed human EPC and ASC cooperatively form mature and stable vasculature with subsequent functional integration into a host vasculature system.

scholarly journals Shapes in the Shadow: Evolutionary Dynamics of Morphogenesis

2000 ◽  
Vol 6 (1) ◽  
pp. 85-101 ◽  
Author(s):  
P. Hogeweg
Keyword(s):  
Cell Differentiation ◽  
Side Effects ◽  
Evolutionary Dynamics ◽  
De Novo ◽  
Cell Types ◽  
Intercellular Signaling ◽  
Punctuated Equilibria ◽  
Constant Rate ◽  
Specific Complex ◽  
Differentiation Pattern

This article investigates the evolutionary dynamics of morphogenesis. In this study, morphogenesis arises as a side-effect of maximization of number of cell types. Thus, it investigates the evolutionary dynamics of side-effects. Morphogenesis is governed by the interplay between differential cell adhesion, gene-regulation, and intercellular signaling. Thus, it investigates the potential to generate complex behavior by entanglement of relatively “boring” processes, and the (automatic) coordination between these processes. The evolutionary dynamics shows all the hallmarks of evolutionary dynamics governed by nonlinear genotype phenotype mapping: for example, punctuated equilibria and diffusion on neutral paths. More striking is the result that interesting, complex morphogenesis occurs mainly in the “shadow” of neutral paths which preserve cell differentiation, that is, the interesting morphologies arise as mutants of the fittest individuals. Characteristics of the evolution of such side-effects in the shadow appear to be the following: (1) The specific complex morphologies are unique (or at least very rare) among the set of de novo initiated evolutionary histories. (2) Similar morphologies are reinvented at large temporal distances during one evolutionary history and also when evolution is restarted after the main cell differentiation pattern has been established. (3) A mosaic-like evolution at the morphological level, where different morphological features occur in many combinations, while at the genotypic level recombination is not implemented and genotypes diverge linearly and at a constant rate.

scholarly journals Induction of De Novo Subcortical Actin Filament Assembly by Treponema denticola Major Outer Sheath Protein

2004 ◽  
Vol 72 (6) ◽  
pp. 3650-3654 ◽  
Author(s):  
Mohsen Amin ◽  
Andy C. S. Ho ◽  
Jenny Y. Lin ◽  
Andre Paes Batista da Silva ◽  
Michael Glogauer ◽  
...  
Keyword(s):  
Actin Filament ◽  
De Novo ◽  
Cell Types ◽  
Treponema Denticola ◽  
Actin Reorganization ◽  
Filament Assembly ◽  
Outer Sheath

ABSTRACT Treponema denticola and its major outer sheath protein (Msp) induce actin reorganization in fibroblasts. We adapted a barbed-end labeling/imaging assay to monitor Msp-induced subcortical actin filament assembly in neutrophils and fibroblasts. Msp, at an actin-reorganizing concentration, inhibited migration of these dissimilar cell types, whose cytoskeletal functions in locomotion and phagocytosis are crucial for immunity and healing of peripheral infections.

scholarly journals Identification of a mesenchymal progenitor cell hierarchy in adipose tissue

Science ◽  
2019 ◽  
Vol 364 (6438) ◽  
pp. eaav2501 ◽  
Author(s):  
David Merrick ◽  
Alexander Sakers ◽  
Zhazira Irgebay ◽  
Chihiro Okada ◽  
Catherine Calvert ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Progenitor Cells ◽  
Transforming Growth Factor ◽  
De Novo ◽  
Mesenchymal Cell ◽  
Transforming Growth Factor Β ◽  
Cell Types ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Dipeptidyl Peptidase 4

Metabolic health depends on the capacity of adipose tissue progenitor cells to undergo de novo adipogenesis. The cellular hierarchy and mechanisms governing adipocyte progenitor differentiation are incompletely understood. Through single-cell RNA sequence analyses, we show that the lineage hierarchy of adipocyte progenitors consists of distinct mesenchymal cell types that are present in both mouse and human adipose tissues. Cells marked by dipeptidyl peptidase–4 (DPP4)/CD26 expression are highly proliferative, multipotent progenitors. During the development of subcutaneous adipose tissue in mice, these progenitor cells give rise to intercellular adhesion molecule–1 (ICAM1)/CD54–expressing (CD54+) committed preadipocytes and a related adipogenic cell population marked by Clec11a and F3/CD142 expression. Transforming growth factor–β maintains DPP4+ cell identity and inhibits adipogenic commitment of DPP4+ and CD142+ cells. Notably, DPP4+ progenitors reside in the reticular interstitium, a recently appreciated fluid-filled space within and between tissues, including adipose depots.

Endothelin synthesis by rabbit renal tubule cells

1991 ◽  
Vol 261 (2) ◽  
pp. F221-F226 ◽  
Author(s):  
D. E. Kohan
Keyword(s):  
High Performance ◽  
Renal Tubule ◽  
De Novo ◽  
Collecting Duct ◽  
Cell Types ◽  
Phospholipid Metabolism ◽  
Thick Ascending Limb ◽  
Medullary Collecting Duct ◽  
Tubule Cells ◽  
Endothelin 3

Endothelins regulate nephron sodium and water transport, prostaglandin E2 (PGE2) synthesis, and phospholipid metabolism. Recent studies suggest that renal tubule cells synthesize endothelins. To determine which nephron sites have such potential, endothelin production by cells derived from different nephron segments was examined. Immunoreactive endothelin 1 (ET-1) and endothelin 3 (ET-3) were measured in supernatants of cultured rabbit proximal tubule (PT), medullary thick ascending limb (MTAL), cortical collecting tubule (CCT), and inner medullary collecting duct (IMCD) cells. All cell types released immunoreactive ET-1 and ET-3. However, the amounts of endothelin produced differed as follows: IMCD greater than MTAL greater than CCT much greater than PT for ET-1 and IMCD greater than MTAL = PT = CCT for ET-3; in all cases ET-1 much greater than ET-3. To confirm de novo ET-3 synthesis, IMCD cells were labeled with [35S]cysteine, and the supernatant was immunoprecipitated with anti-ET-3 antibody. Sample and standard ET-3 eluted at identical positions on high-performance liquid chromatographs, confirming de novo synthesis of ET-3 by cultured IMCD cells. These data raise the possibility of an important functional role for nephron-derived endothelin and, in particular, endothelin produced by tubule cells in the medulla.

scholarly journals Cytosolic chaperones mediate quality control of higher-order septin assembly in budding yeast

2015 ◽  
Vol 26 (7) ◽  
pp. 1323-1344 ◽  
Author(s):  
Courtney R. Johnson ◽  
Andrew D. Weems ◽  
Jennifer M. Brewer ◽  
Jeremy Thorner ◽  
Michael A. McMurray
Keyword(s):  
Quality Control ◽  
De Novo ◽  
Cell Types ◽  
Binding Pocket ◽  
Sole Source ◽  
Eukaryotic Cell ◽  
Higher Order ◽  
Native Proteins ◽  
Wild Type Counterpart ◽  
Quality Control Mechanism

Septin hetero-oligomers polymerize into cytoskeletal filaments with essential functions in many eukaryotic cell types. Mutations within the oligomerization interface that encompasses the GTP-binding pocket of a septin (its “G interface”) cause thermoinstability of yeast septin hetero-oligomer assembly, and human disease. When coexpressed with its wild-type counterpart, a G interface mutant is excluded from septin filaments, even at moderate temperatures. We show that this quality control mechanism is specific to G interface mutants, operates during de novo septin hetero-oligomer assembly, and requires specific cytosolic chaperones. Chaperone overexpression lowers the temperature permissive for proliferation of cells expressing a G interface mutant as the sole source of a given septin. Mutations that perturb the septin G interface retard release from these chaperones, imposing a kinetic delay on the availability of nascent septin molecules for higher-order assembly. Un­expectedly, the disaggregase Hsp104 contributes to this delay in a manner that does not require its “unfoldase” activity, indicating a latent “holdase” activity toward mutant septins. These findings provide new roles for chaperone-mediated kinetic partitioning of non-native proteins and may help explain the etiology of septin-linked human diseases.

Sign in / Sign up

Export Citation Format

Share Document