Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Biosynthesis and transport of lysosomal enzymes in human monocytes and macrophages. Effects of ammonium chloride, zymosan and tunicamycin.

ABSTRACT: Human monocytes and macrophages synthesize lysosomal enzymes as larger precursors. The polypeptide patterns of several lysosomal-enzyme precursors and their mature forms are similar to those observed in human fibroblasts. Like fibroblasts, the monocytes and macrophages release small amounts of lysosomal-enzyme precursors. The lysosomotropic NH4+ cation enhances this release. In contrast, zymosan, a degranulating agent, causes release of both the mature and the precursor forms of the lysosomal enzymes. Both NH4Cl and zymosan inhibit maturation of the precursors. The fractional amounts of mature cathepsin D and beta-hexosaminidase released in the presence of zymosan are strikingly different. Probably, in the macrophages several lysosomal organelles are packaged with different relative contents of lysosomal enzymes. The transport of the precursors of cathepsin D into lysosomes is inhibited by tunicamycin. Therefore oligosaccharide side chains are likely to function as signals in packaging of lysosomal enzymes in macrophages also.

SUBMITTER: Imort M

PROVIDER: S-EPMC1152302 | biostudies-other | 1983 Sep

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

Glucan receptor and zymosan-induced lysosomal enzyme secretion in macrophages.

Project description:A receptor for beta-glucan was in the present study shown to mediate binding of zymosan particles to resident mouse peritoneal macrophages. Lysosomal enzyme secretion in response to zymosan was maximal at a low particle/cell ratio, continuous for at least 3 h after particle/cell contact and inhibitable by soluble glucan. Latex particles of various size caused no selective secretory response, but at high particle/cell ratios were toxic. By use of a fluorescent ligand, the macrophage beta-glucan receptor was shown to be trypsin-sensitive, Ca2+/Mg(2+)-independent, recirculating and also present in an intracellular mobilizable pool. Binding of ligand to the beta-glucan receptor and inhibition of the lysosomal secretory response to zymosan were both more efficient with glucans of larger size, indicating that clustering of glucan receptors at the cell surface occurs. Such clustering could stabilize ligand binding by multiple interactions and possibly trigger intracellular signaling events on binding of zymosan particles.

| S-EPMC1136595 | biostudies-other

Lysosomal storage disease upon disruption of the neuronal chloride transport protein ClC-6.

Project description:Mammalian CLC proteins function as Cl(-) channels or as electrogenic Cl(-)/H(+) exchangers and are present in the plasma membrane and intracellular vesicles. We now show that the ClC-6 protein is almost exclusively expressed in neurons of the central and peripheral nervous systems, with a particularly high expression in dorsal root ganglia. ClC-6 colocalized with markers for late endosomes in neuronal cell bodies. The disruption of ClC-6 in mice reduced their pain sensitivity and caused moderate behavioral abnormalities. Neuronal tissues showed autofluorescence at initial axon segments. At these sites, electron microscopy revealed electron-dense storage material that caused a pathological enlargement of proximal axons. These deposits were positive for several lysosomal proteins and other marker proteins typical for neuronal ceroid lipofuscinosis (NCL), a lysosomal storage disease. However, the lysosomal pH of Clcn6(-/-) neurons appeared normal. CLCN6 is a candidate gene for mild forms of human NCL. Analysis of 75 NCL patients identified ClC-6 amino acid exchanges in two patients but failed to prove a causative role of CLCN6 in that disease.

| S-EPMC1564226 | biostudies-literature

Cellular transport of lysosomal enzymes: an alternative hypothesis.

Project description:Hickman & Neufeld [(1972) Biochem, Biophys. Res. Commun. 49, 992-999] have proposed that lysosomal enzymes reach the lysosomes by means of exocytosis and subsequent pinocytic reincorporation. The results leading to this conclusion are re-assessed and an alternative explanation is advanced that relates to the necessity for membrane recycling in endocytic cells.

| S-EPMC1164786 | biostudies-other

(Methyldiphenyl-phospho-ranylidene)-ammonium chloride.

Project description:The title compound, C(13)H(15)NP(+)·Cl(-), was obtained by hydrolysis of the N-trimethysilyl derivative of methydiphenyl-imino-phosphine. The dihedral angle between the phenyl rings in the cation is 61.5?(3)°. In the crystal structure, inter-molecular N-H?Cl hydrogen bonds links the two components, forming a centrosymmetric 2 + 2 aggregate.

| S-EPMC2969268 | biostudies-literature

Zymosan-mediated inflammation impairs in vivo reverse cholesterol transport.

Project description:Inflammation has been proposed to impair HDL function and reverse cholesterol transport (RCT). We investigated the effects of inflammation mediated by zymosan, a yeast glucan, on multiple steps along the RCT pathway in vivo and ex vivo. Acute inflammation with 70 mg/kg zymosan impaired RCT to plasma, liver, and feces similarly by 17-22% (P < 0.05), with no additional block at the liver. Hepatic gene expression further demonstrated no change in ABCG5, ABCB4, and ABCB11 expression but a decline in ABCG8 mRNA (32% P < 0.05). Plasma from zymosan-treated mice had a 21% decrease in cholesterol acceptor ability (P < 0.01) and a 35% decrease in ABCA1-specific efflux capacity (P < 0.01) in vitro. Zymosan treatment also decreased HDL levels and led to HDL remodeling with increased incorporation of serum amyloid A. In addition, cholesterol efflux from cultured macrophages declined with zymosan treatment in a dose dependent manner. Taken together, our results suggest that zymosan impairs in vivo RCT primarily by decreasing macrophage-derived cholesterol entering the plasma, with minimal additional blocks downstream. Our study supports the notion that RCT impairment is one of the mechanisms for the increased atherosclerotic burden observed in inflammatory conditions.

| S-EPMC3073469 | biostudies-literature

Primary amines induce selective release of lysosomal enzymes from mouse macrophages.

Project description:Cultured mouse peritoneal macrophages were found to release substantial amounts of lysosomal beta-glucuronidase and beta-glactosidase activites when exposed to millimolar concentrations of various primary aliphatic monoamines. With methylamine, ethylamine, propylamine and butylamine, lysosomal enzyme release was selective, but further increases in the aliphatic chain length resulted in the compounds becoming lytic. By contrast, structurally related primary aliphatic diamines proved to be inactive at inducing both selective and lytic lysosomal-enzyme discharge.

| S-EPMC1161981 | biostudies-other

(1-Naphthyl-meth-yl)ammonium chloride.

Project description:The reaction of 1-naphthyl-methyl-amine and hydro-chloric acid in a 1:1 molar ratio resulted in the formation of the 1:1 proton-transfer compound, C(11)H(12)N(+)·Cl(-). In the crystal, the ions are linked by N-H?Cl hydrogen bonds into a sheet pattern in the ab plane such that each Cl(-) ion is bonded to three NH groups from the naphthylmethylammonium ion.

| S-EPMC2983625 | biostudies-literature

N-Hydroxy-N-methyl-ammonium chloride.

Project description:In the crystal structure of the title compound, CH(6)NO(+)·Cl(-), the cations and anions are linked by N-H?Cl and O-H?Cl hydrogen bonds into an undulating layer motif [Schläfli symbol: 4(8).6(8).8(2)]. All non-H atoms lie on a mirror plane.

| S-EPMC2961632 | biostudies-literature

Tetra-n-propyl-ammonium chloride monohydrate.

Project description:The crystal structure of the title salt hydrate, C(12)H(28)N(+)·Cl(-)·H(2)O, consists of non-inter-acting cations and anions. The water mol-ecule forms hydrogen bonds to two chloride ions, about a center of inversion, generating a planar eight-membered {⋯H-O-H⋯Cl}(2) ring.

| S-EPMC2969089 | biostudies-literature

Glutamine Produces Ammonium to Tune Lysosomal pH and Regulate Lysosomal Function.

Project description:Glutamine is one of the most abundant amino acids in the cell. In mitochondria, glutaminases 1 and 2 (GLS1/2) hydrolyze glutamine to glutamate, which serves as the precursor of multiple metabolites. Here, we show that ammonium generated during GLS1/2-mediated glutaminolysis regulates lysosomal pH and in turn lysosomal degradation. In primary human skin fibroblasts BJ cells and mouse embryonic fibroblasts, deprivation of total amino acids for 1 h increased lysosomal degradation capacity as shown by the increased turnover of lipidated microtubule-associated proteins 1A/1B light chain 3B (LC3-II), several autophagic receptors, and endocytosed DQ-BSA. Removal of glutamine but not any other amino acids from the culture medium enhanced lysosomal degradation similarly as total amino acid starvation. The presence of glutamine in regular culture media increased lysosomal pH by >0.5 pH unit and the removal of glutamine caused lysosomal acidification. GLS1/2 knockdown, GLS1 antagonist, or ammonium scavengers reduced lysosomal pH in the presence of glutamine. The addition of glutamine or NH4Cl prevented the increase in lysosomal degradation and curtailed the extension of mTORC1 function during the early time period of amino acid starvation. Our findings suggest that glutamine tunes lysosomal pH by producing ammonium, which regulates lysosomal degradation to meet the demands of cellular activities. During the early stage of amino acid starvation, the glutamine-dependent mechanism allows more efficient use of internal reserves and endocytosed proteins to extend mTORC1 activation such that the normal anabolism is not easily interrupted by a brief disruption of the amino acid supply.

| S-EPMC9819001 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data