Involvement of Early and Late Lysosomes in the Degradation of Mannosylated Ligands by Rat Liver Endothelial Cells

Kjeken, Rune; Brech, Andreas; Løvdal, Torunn; Roos, Norbert; Berg, Trond

doi:10.1006/excr.1995.1037

Cited by 18 publications

(16 citation statements)

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“…These small vesicles are probably early endosomes reminiscent of small bristle coated vesicles that have been previously observed electron microscopically as vesicles with a diameter of 180 nm, located directly below the cell surface [39]. The vesicles containing FITC-bHA after a 10 min pulse at 37°C followed by a 20 min chase, are probably late endosomes (with diameter ranging between 800–1500 nm) as reported in similar studies in rat LSEC [38,39]. After a 2 h chase, the stain partly co-localized with TRITC-FSA, indicating further transport to late endosomes and lysosomes.…”

Section: Discussionsupporting

confidence: 67%

“…Competition experiments showed that the ligands were taken up in a specific manner, via the five different categories of receptors. Moreover, morphologic pulse-chase experiments using FITC-labelled ligands to study the intracellular transport of endocytosed ligand suggested that all ligands studied, with the exception of AGG, reached lysosomal compartments within a time span of 2 h. At that time, AGG was still found in ring shaped structures which is a typical feature of early and late endosomes [33,38]. The finding that endocytosed AGG was degraded (albeit not as efficiently as other ligands), without reaching the lysosomal compartment, indicates that this ligand is processed differently than the other ligands studied.…”

Section: Discussionmentioning

confidence: 99%

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et al. 2004

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Background: The liver sinusoidal endothelial cells (LSEC) and Kupffer cells constitute the most powerful scavenger system in the body. Various waste macromolecules, continuously released from tissues in large quantities as a consequence of normal catabolic processes are cleared by the LSEC. In spite of the fact that pig livers are used in a wide range of experimental settings, the scavenger properties of pig LSEC has not been investigated until now. Therefore, we studied the endocytosis and intracellular transport of ligands for the five categories of endocytic receptors in LSEC.

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Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 99%

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et al. 2004

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“…The conventional picture of the lysosomal degradation of extracellular cargo describes internalization of cargo from the plasma membrane, transport from early to late endosomes, and delivery of cargo to the lysosome, an acidic, enzyme-rich, membrane-bound organelle [5]–[7]. In recent years, a more complex picture of lysosomal degradation has emerged that demonstrates degradation can occur upstream of lysosomes and that key lysosomal proteins are not necessary for the degradation of extracellular cargo [8]–[13]. Reconciling these results with the conventional picture of the endo-lysosomal pathway has taken on increasing importance with the advent of gene delivery and nanobiotechnology, fields in which delivery of DNA or nanoparticles to enzyme-rich, degradative vesicles is either targeted for triggered release or avoided to prevent degradation [14], [15].…”

Section: Introductionmentioning

confidence: 99%

Endo-Lysosomal Vesicles Positive for Rab7 and LAMP1 Are Terminal Vesicles for the Transport of Dextran

2011

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The endo-lysosomal pathway is essential for intracellular transport and the degradation of extracellular cargo. The relationship between three populations of endo-lysosomal vesicles—Rab7-positive, LAMP1-positive, and both Rab7- and LAMP1-postive—was probed with fluorescence microscopy and single particle tracking. Of specific interest was determining if these vesicles were intermediate or terminal vesicles in the transport of extracellular cargo. We find that the major organelle in the endo-lysosomal pathway, both in terms of population and cargo transport, is positive for Rab7 and LAMP1. Dextran, a fluid phase cargo, shifts from localization within all three populations of vesicles at 30 minutes and 1 hour to primarily LAMP1- and Rab7/LAMP1-vesicles at longer times. This demonstrates that LAMP1- and Rab7/LAMP1-vesicles are terminal vesicles in the endo-lysosomal pathway. We tested two possible mechanisms for this distribution of cargo, delivery to mannose 6-phosphate receptor (M6PR)-negative vesicles and the fusion dynamics of individual vesicles. We find no correlation with M6PR but do find that Rab7-vesicles undergo significantly fewer fusion events than LAMP1- or Rab7/LAMP1-vesicles suggesting that the distribution of fluid phase cargo is driven by vesicle dynamics.

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“…The higher density of the radioactivity peak compared with the lysosomal marker peak in the younger animals can also be explained by tracer localisation in different subclasses of lysosomes. Breakdown of poorly degradable material takes place in late or terminal lysosomes (Kjeken et al, 1995). Incomplete digestion causes undigested material to accumulate and generate residual bodies, also called tertiary lysosomes, or dense bodies (Nixon and Cataldo, 1993; Schmucker and Sachs, 2002) that are denser than lysosomes (Roederer et al, 1989; Rome et al, 1979).…”

Section: Discussionmentioning

confidence: 99%

Hepatic disposal of advanced glycation end products during maturation and aging

Svistounov

Oteiza

Zykova

et al. 2013

Experimental Gerontology

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Aging is characterized by progressive loss of metabolic and biochemical functions and accumulation of metabolic by-products, including advanced glycation end products (AGEs), which are observed in several pathological conditions. A number of waste macromolecules, including AGEs are taken up from the circulation by endocytosis mainly into liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs). However, AGEs still accumulate in different tissues with ageing, despite the presence of this clearance mechanism. The aim of the present study was to determine whether the efficiency of LSECs and KCs for disposal of AGEs changes through aging. Results After intravenous administration of 14C-AGE-albumin in pre-pubertal, young adult, middle aged and old mice, more than 90% of total recovered 14C-AGE was liver associated, irrespective of age. LSECs and KCs represented the main site of uptake. A fraction of the 14C-AGE degradation products (14C-AGE-DPs) was stored for months in the lysosomes of these cells after uptake. The overall rate of elimination of 14C-AGE-DPs from the liver was markedly faster in pre-pubertal than in all post-pubertal age groups. The ability to eliminate 14C-AGE-DPs decreased to similar extents after puberty in LSECs and KCs. A rapid early removal phase was characteristic for all age groups except the old group, where this phase was absent. Conclusions Removal of AGE-DPs from the liver scavenger cells is a very slow process that changes with age. The ability of these cells to dispose of AGEs declines after puberty. Decreased AGE removal efficiency early in life may lead to AGE accumulation.

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Involvement of Early and Late Lysosomes in the Degradation of Mannosylated Ligands by Rat Liver Endothelial Cells

Cited by 18 publications

References 0 publications

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Endo-Lysosomal Vesicles Positive for Rab7 and LAMP1 Are Terminal Vesicles for the Transport of Dextran

Hepatic disposal of advanced glycation end products during maturation and aging

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