scholarly journals Specific alterations in levels of mannose 6-phosphorylated glycoproteins in different neuronal ceroid lipofuscinoses

1998 ◽  
Vol 334 (3) ◽  
pp. 547-551 ◽  
Author(s):  
David E. SLEAT ◽  
Istvan SOHAR ◽  
Premila S. PULLARKAT ◽  
Peter LOBEL ◽  
Raju K. PULLARKAT
Keyword(s):  
Lysosomal Enzyme ◽  
Neurodegenerative Disorders ◽  
Enzyme Activities ◽  
Lysosomal Enzymes ◽  
Vesicular Transport ◽  
Cell Types ◽  
Neuronal Ceroid Lipofuscinoses ◽  
Mannose 6 Phosphate ◽  
Normal Controls ◽  
Lysosomal Proteins

Mannose 6-phosphate (Man-6-P) is a carbohydrate modification that is generated on newly synthesized lysosomal proteins. This modification is specifically recognized by two Man-6-P receptors that direct the vesicular transport of the lysosomal enzymes from the Golgi to a prelysosomal compartment. The Man-6-P is rapidly removed in the lysosome of most cell types; however, in neurons the Man-6-P modification persists. In this study we have examined the spectrum of Man-6-P-containing glycoproteins in brain specimens from patients with different neuronal ceroid lipofuscinoses (NCLs), which are progressive neurodegenerative disorders with established links to defects in lysosomal catabolism. We find characteristic alterations in the Man-6-P glycoproteins in specimens from late-infantile (LINCL), juvenile (JNCL) and adult (ANCL) patients. Man-6-P glycoproteins in LINCL patients were similar to controls, with the exception that the band corresponding to CLN2, a recently identified lysosomal enzyme whose deficiency results in this disease, was absent. In an ANCL patient, two Man-6-P glycoproteins were elevated in comparison with normal controls, suggesting that this disease also results from a perturbation in lysosomal hydrolysis. In JNCL, total levels of Man-6-P glycoproteins were 7-fold those of controls. In general this was reflected by increased lysosomal enzyme activities in JNCL but three Man-6-P glycoproteins were elevated to an even greater degree. These are CLN2 and the unidentified proteins that are also highly elevated in the ANCL.

scholarly journals Mouse mutants lacking the cation-independent mannose 6-phosphate/insulin-like growth factor II receptor are impaired in lysosomal enzyme transport: comparison of cation-independent and cation-dependent mannose 6-phosphate receptor-deficient mice

1998 ◽  
Vol 330 (2) ◽  
pp. 903-908 ◽  
Author(s):  
Istvan SOHAR ◽  
David SLEAT ◽  
Chang-Gong LIU ◽  
Thomas LUDWIG ◽  
Peter LOBEL
Keyword(s):  
Growth Factor ◽  
Lysosomal Enzyme ◽  
Enzyme Activities ◽  
Lysosomal Enzymes ◽  
Insulin Like Growth Factor ◽  
Factor Ii ◽  
Solid Tissues ◽  
Mannose 6 Phosphate ◽  
Deficient Mice

Two proteins have been implicated in the mannose 6-phosphate-dependent transport of lysosomal enzymes to lysosomes: the 300 kDa cation-independent and the 46 kDa cation-dependent mannose 6-phosphate receptors (CI- and CD-MPRs). The mammalian CI-MPR also mediates endocytosis and clearance of insulin-like growth factor II (IGF-II). Mutant mice that lack the CD-MPR are viable, mice that lack the CI-MPR accumulate high levels of IGF-II and usually die perinatally, whereas mice that lack both IGF-II and CI-MPR are viable. To investigate the relative roles of the MPRs in the targeting of lysosomal enzymes in vivo, we analysed the effect of a deficiency of either MPR on lysosomal enzyme activities in animals lacking IGF-II. In CD-MPR-deficient mice, most activities were relatively normal in solid tissues and some were marginally elevated in serum. In CI-MPR-deficient mice, some enzyme activities were moderately decreased in solid tissues and multiple enzymes were markedly elevated in serum. Finally, total levels of serum mannose 6-phosphorylated glycoproteins were ~ 45-fold and ~ 15-fold higher than wild type in CI- and CD-MPR-deficient mice respectively, and there were specific differences in the pattern of these proteins when comparing CI- and CD-MPR deficient animals. These results indicate that while lack of the CI-MPR appears to perturb lysosome function to a greater degree than lack of the CD-MPR, each MPR has distinct functions for the targeting of lysosomal enzymes in vivo.

Mannose 6-phosphate receptor-dependent endocytosis of lysosomal enzymes is increased in sulfatide-storing kidney cells

2009 ◽  
Vol 390 (1) ◽  
Author(s):  
Diana Klein ◽  
Afshin Yaghootfam ◽  
Ullrich Matzner ◽  
Bettina Koch ◽  
Thomas Braulke ◽  
...  
Keyword(s):  
Lysosomal Enzymes ◽  
Cell Types ◽  
Recycling Rate ◽  
Kidney Cells ◽  
Lysosomal Disorder ◽  
Renal Tubular Cells ◽  
Internalization Rate ◽  
Mannose 6 Phosphate ◽  
Renal Tubular ◽  
Kinetics Of

Abstract Metachromatic leukodystrophy is a lysosomal disorder caused by the deficiency of arylsulfatase A (ASA). This leads to the storage of the sphingolipid 3-O-sulfogalactosylceramide (sulfatide) in various cell types, such as renal tubular cells. Examination of mannose 6-phosphate receptor (MPR300)-dependent endocytosis revealed that uptake of lysosomal enzymes is more than two-fold increased in sulfatide-storing kidney cells. Expression of MPR300 and its internalization rate is increased in these cells, whereas the recycling rate is decreased. Similar alterations can be found for the transferrin receptor, indicating that sulfatide storage leads to a general alteration of the endocytotic pathway. These data allow calculating that the endosomal pool from which receptors can recycle is 1.4- to 2-fold increased in lipid-storing cells. Immunocytochemistry demonstrates that the MPR300 in lipid-storing cells does not co-localize with accumulated sulfatide, suggesting that the kinetics of internalization and recycling appear to be altered indirectly.

scholarly journals Proteolytische Aktivitäten der lysosomalen Enzyme bei Milchrindern* – 1. Mitteilung: Variation der lysosomalen Enzyme bei Milchkühen

1999 ◽  
Vol 42 (4) ◽  
pp. 321-334
Author(s):  
L. Panicke ◽  
M. Schmidt ◽  
T. Król ◽  
R. Staufenbiel
Keyword(s):  
Dairy Cattle ◽  
Lysosomal Enzyme ◽  
Enzyme Activities ◽  
Lysosomal Enzymes ◽  
Milk Traits ◽  
Additional Information ◽  
Milk Performance ◽  
Proteolytic Activities ◽  
Fertility Traits ◽  
Daily Milk

Abstract. Titel of the paper: Proteolytic activities of lysosomal enzymes in dairy cattle. I. Variation of lysosomal enzymes in dairy cattle There are no references to be found in the literature dealing with genetic aspects of lysosomal enzyme activities m blood of dairy cows, The used amino peptidases are connected to the proteolysis. 1011 investigated cows showed Variation coefficients of ≈50%, higher than in milk traits In simultaneous samples it reduces to 20–30% similar to daily milk samples The heritability coefficients h2 = 0,10–0,20 is approximately between fertility traits and milk traits The investigation of lysosomal enzyme activities might be limited to plasma. No additional information could be gained using the leukocytes. Changing activities of enzymes in plasma are aqually directed to the milk performance. It may be concluded that the trait spectrum might be reduced to DP-IV, AGR, ALA, AGLD and EL as well especially to protein yield of milk.

Lysosomal Enzyme Activities in Platelets of Normal Individuals and of Patients with Gaucher’s Disease

1974 ◽  
Vol 32 (02/03) ◽  
pp. 665-669 ◽  
Author(s):  
S Yatziv ◽  
M White ◽  
A Eldor
Keyword(s):  
Acid Phosphatase ◽  
Lysosomal Enzyme ◽  
Enzyme Activities ◽  
The Other ◽  
Gaucher's Disease ◽  
Gaucher’S Disease ◽  
Other Hand ◽  
Normal Individuals ◽  
Specific Activities ◽  
Normal Controls

SummaryFive platelet lysosomal enzyme activities were estimated in 22 normal individuals and in 5 patients with Gaucher’s disease: ß-D-galactosidase, N-Acetyl-ß-D-glucosa-minidase, N-Acetyl-ß-D-galactosaminidase acid-phosphatase, and ß-D-glucuronidase.In the 5 patients with Gaucher’s disease the specific activities for the first four of these enzymes were significantly higher than in normal individuals. The activity of acid-phosphatase, on the other hand, was lower in G. d. than in normals. The release of the 5 lysosomal enzymes from platelets upon incubation with thrombin was also examined in the same two groups. The only lysosomal enzyme that was not released from normal platelets was acid-phosphatase. In Gaucher’s patients, on the other hand, acid-phosphatase was invariably released from platelets when incubated with thrombin. The release of the other four enzymes from platelets of Gaucher patients was similar to that of normal controls.

Alterations in cardiac lysosomal hydrolases following induction of the calcium paradox

1987 ◽  
Vol 65 (11) ◽  
pp. 2175-2181 ◽  
Author(s):  
Michael J. B. Kutryk ◽  
Naranjan S. Dhalla
Keyword(s):  
Lysosomal Enzyme ◽  
Enzyme Activities ◽  
Lysosomal Enzymes ◽  
Cell Damage ◽  
Calcium Paradox ◽  
Free Medium ◽  
Lysosomal Hydrolases ◽  
Cardiac Damage ◽  
Rat Hearts ◽  
Reperfusion Period

Although perfusion of the heart with calcium-free medium for a brief period followed by reperfusion with calcium-containing medium results in marked structural derangements (calcium paradox), the mechanisms for this cell damage are far from clear. Since activation of lysosomal enzymes has been associated with pathological damage, it was the purpose of this study to examine alterations in the activities of several lysosomal enzymes in rat hearts subjected to calcium paradox. No significant changes in the activities of (β-acetylglucosaminidase, β-galactosidase, α-mannosidase, or acid phosphatase were seen in the homogenates of hearts exposed to the calcium paradox. However, there were dramatic alterations in the lysosomal enzyme activities in the sedimentable and nonsedimentable fractions during calcium paradox. The lysosomal enzyme activities were also detected in the perfusate collected during reperfusion with calcium-containing medium. These changes occurred during the reperfusion period since no alterations were apparent after calcium-free perfusion and were dependent upon the time of reperfusion with medium containing Ca2+ as well as the time of perfusion with Ca2+ -free medium before inducing Ca2+ paradox. These data indicate that alterations in lysosomal enzymes owing to reinstitution of calcium in Ca2+-deprived hearts may occur as a part of cardiac damage and general cellular disintegration.

scholarly journals Regulation of macrophage lysosomal enzyme secretion: role of arachidonate metabolites, divalent cations and cyclic AMP

1980 ◽  
Vol 44 (1) ◽  
pp. 299-315
Author(s):  
R.M. McMillan ◽  
D.E. Macintyre ◽  
J.E. Beesley ◽  
J.L. Gordon
Keyword(s):  
Cyclic Amp ◽  
Lysosomal Enzyme ◽  
Lysosomal Enzymes ◽  
Divalent Cations ◽  
Cell Types ◽  
Enzyme Secretion ◽  
Ionophore A23187 ◽  
Enzyme Release ◽  
Arachidonate Metabolites

We have investigated the role in macrophage lysosomal enzyme release of arachidonate metabolites, extracellular divalent cations and cyclic AMP (cAMP) which modulate secretion in other cell types. Lysosomal enzyme secretion induced by zymosan was accompanied by release of malondialdehyde (MDA), which is derived from arachidonic acid via prostaglandin synthase. Blockade of MDA formation, by aspirin or indomethacin, was associated with only a small inhibitory effect on lysosomal enzyme release by zymosan: arachidonate metabolites thus play only a minor role in mediating macrophage lysosomal enzyme release. Zymosan-induced secretion of lysosomal enzymes from macrophages did not require extracellular magnesium or calcium although release was enhanced by magnesium and inhibited by calcium. These effects may be related to an influence of the ions on phagocytosis. Elevation of intracellular divalent cation concentrations, by ionophore A23187, induced release of lysosomal enzymes but this was a result of cell lysis. Adenylate cyclase stimulants and dibutyryl cAMP produced slight inhibition of zymosan-induced lysosomal enzyme release. Aminophylline and papaverine caused more marked inhibition but their effects may be due to actions independent of phosphodiesterase inhibition. Our data indicate that arachidonate metabolites and cAMP do not play a major role in regulating zymosan-induced enzyme release from macrophages. Extracellular calcium and magnesium may modulate secretion but the role of intracellular divalent cations remains to be established. We conclude that macrophage lysosomal enzyme secretion is controlled by regulatory mechanisms different from those which control similar degranulation processes in other cell types.

Dictyostelium lysosomal proteins with different sugar modifications sort to functionally distinct compartments

1997 ◽  
Vol 110 (18) ◽  
pp. 2239-2248 ◽  
Author(s):  
G.M. Souza ◽  
D.P. Mehta ◽  
M. Lammertz ◽  
J. Rodriguez-Paris ◽  
R. Wu ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Lysosomal Enzymes ◽  
Cysteine Proteinases ◽  
Retrieval Mechanism ◽  
Mannose 6 Phosphate ◽  
Lysosomal Proteins

Many Dictyostelium lysosomal enzymes contain mannose-6-phosphate (Man-6-P) in their N-linked oligosaccharide chains. We have now characterized a new group of lysosomal proteins that contain N-acetylglucosamine-1-phosphate (GlcNAc-1-P) linked to serine residues. GlcNAc-1-P-containing proteins, which include papain-like cysteine proteinases, cofractionate with the lysosomal markers and are in functional vesicles of the endosomal/lysosomal pathway. Immunoblots probed with reagents specific for each carbohydrate modification indicate that the lysosomal proteins are modified either by Man-6-P or GlcNAc-1-P, but not by both. Confocal microscopy shows that the two sets of proteins reside in physically and functionally distinct compartments. Vesicles with GlcNAc-1-P fuse with nascent bacteria-loaded phagosomes less than 3 minutes after ingestion, while those with Man-6-P do not participate in bacterial digestion until about 15 minutes after phagocytosis. Even though both types of vesicles fuse with phagosomes, GlcNAc-1-P- and Man-6-P-bearing proteins rarely colocalize. Since both lysosomal enzymes and their bound carbohydrate modifications are stable in lysosomes, a targeting or retrieval mechanism based on these carbohydrate modifications probably establishes and/or maintains segregation.

scholarly journals Defective lysosomal enzyme secretion in kidneys of Chediak-Higashi (beige) mice.

1975 ◽  
Vol 67 (3) ◽  
pp. 774-788 ◽  
Author(s):  
E J Brandt ◽  
R W Elliott ◽  
R T Swank
Keyword(s):  
Lysosomal Enzyme ◽  
Lysosomal Enzymes ◽  
Cell Types ◽  
Subcellular Fractionation ◽  
Histochemical Staining ◽  
Beige Mouse ◽  
Androgen Treatment ◽  
Chediak Higashi Syndrome ◽  
Enzyme Elevation ◽  
Enzyme Markers

The beige mouse is an animal model for the human Chediak-Higashi syndrome, a disease characterized by giant lysosomes in most cell types. In mice, treatment with androgenic hormones causes a 20-50-fold elevation in at least one kidney lysosomal enzyme, beta-glucuronidase. Beige mice treated with androgen had significantly higher kidney beta-glucuronidase, beta-galactosidase, and N-acetyl-beta-D-glucosaminidase (hexosaminidase) levels than normal mice. Other androgen-inducible enzymes and enzyme markers for the cytosol, mitochondria, and peroxisomes were not increased in kidney of beige mice. No significant lysosomal enzyme elevation was observed in five other organs of beige mice with or without androgen treatment, nor in kidneys of beige females not treated with androgen. Histochemical staining for glucuronidase together with subcellular fractionation showed that the higher glucuronidase content of beige mouse kidney is caused by a striking accumulation of giant glucuronidase-containing lysosomes in tubule cells near the corticomedullary boundary. In normal mice lysosomal enzymes are coordinately released into the lumen of the kidney tubules and appreciable amounts of lysosomal enzymes are present in the urine. Levels of urinary lysosomal enzymes are much lower in beige mice than in normal mice. It appears that lysosomes may accumulate in beige mice because of defective exocytosis resulting either from decreased intracellular motility of lysosomes or from their improper fusion with the plasma membrane. A similar defect could account for characteristics of the Chediak-Higashi syndrome.

scholarly journals The selective release of phospholipase A2 by resident mouse peritoneal macrophages

1981 ◽  
Vol 200 (2) ◽  
pp. 441-444 ◽  
Author(s):  
P D Wightman ◽  
M E Dahlgren ◽  
P Davies ◽  
R J Bonney
Keyword(s):  
Phospholipase A2 ◽  
Phospholipase C ◽  
Lysosomal Enzyme ◽  
Enzyme Activities ◽  
Lysosomal Enzymes ◽  
Culture Medium ◽  
Peritoneal Macrophages ◽  
Cellular Activity ◽  
Mouse Peritoneal Macrophages ◽  
Phospholipase A2 Activity

Resident mouse peritoneal macrophages have three phospholipase activities: a phospholipase A2 active at pH 4.5, a Ca2+-dependent phospholipase A2 active at pH 8.5 and a phosphatidylinositol-specific phospholipase C activity. When macrophages are exposed to zymosan in culture, the cellular activity of pH-4.5 phospholipase A2 is diminished in a manner dependent on zymosan concentration and time of exposure, whereas the cellular activities of pH-8.5 phospholipase A2 and phospholipase C remain unchanged. The depletion of pH-4.5 phospholipase A2 activity from the cell is paralleled by a quantitative recovery of this activity in the culture medium in a manner similar to the cellular depletion and extracellular recovery of two lysosomal enzymes. This release is specifically elicited by an inflammatory substance such as zymosan, since macrophages incubated with 6 micrometer latex spheres retain pH-4.5 phospholipase A2 activity and lysosomal enzyme activities intracellularly.

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