Hydrolases and cellular death

Lancker, Julien L. Van

doi:10.1007/978-94-011-6618-8_3

Cited by 5 publications

(5 citation statements)

References 16 publications

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“…companies endocytosis by phagocytic cells (5,41), exposure to immobilized immune complexes (10), and lysis of necrotic cells (40). When released extracellularly, lysosomal enzymes may damage surrounding tissues and trigger an acute inflammatory response (16).…”

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confidence: 99%

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Dissociation of intracellular lysosomal rupture from the cell death caused by silica

Kane¹,

Stanton²,

Raymond³

et al. 1980

The Journal of Cell Biology

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The relationship between intracellular lysosomal rupture and cell death caused by silica was studied in P388D, macrophages. After 3 h of exposure to 150 Jig silica in medium containing 1 .8 mM Ca", 60% of the cells were unable to exclude trypan blue . In the absence of extracellular Ca", however, all of the cells remained viable . Phagocytosis of silica particles occurred to the same extent in the presence or absence of Ca" . The percentage of P388D, cells killed by silica depended on the dose and the concentration of Ca" in the medium . Intracellular lysosomal rupture after exposure to silica was measured by acridine orange fluorescence or histochemical assay of horseradish peroxidase . With either assay, 60% of the cells exposed to 150 Ftg silica for 3 h in the presence or absence of Ca" showed intracellular lysosomal rupture, whereas cell death occurred only in the presence of Ca" . Intracellular lysosomal rupture was not associated with measurable degradation of total DNA, RNA, protein, or phospholipid or accelerated turnover of exogenous horseradish peroxidase . Pretreatment with promethazine (20 pg/ml) protected 80% of P388D, macrophages against silica toxicity although lysosomal rupture occurred in 60-70% of the cells. Intracellular lysosomal rupture was prevented in 80% of the cells by pretreatment with indomethacin (5 x 10 -5 M), yet 40-50% of the cells died after 3 h of exposure to 150 p,g silica in 1 .8 mM extracellular Ca" . The calcium ionophore A23187 also caused intracellular lysosomal rupture in 90-98% of the cells treated for 1 h in either the presence or absence of extracellular Ca t+ . With the addition of 1 .8 mM Ca 2+, 80% of the cells was killed after 3 h, whereas all of the cells remained viable in the absence ofCa". These experiments suggest that intracellular lysosomal rupture is not causally related to the cell death caused by silica or A23187 . Cell death is dependent on extracellular Ca 2+ and may be mediated by an influx of these ions across the plasma membrane permeability barrier damaged directly by exposure to these toxins .Lysosomes participate in the physiological turnover of cellular macromolecules (15), limited autophagy of cellular organelles, and storage of undegradable materials (13). At least 60 different enzymes capable of digesting nucleic acids, proteins, lipids, and carbohydrates (6) are contained in these membrane-bound organelles, separated from their potential substrates. Endogenous or exogenous substances enter the lysosome by fusion of autophagic (13) or endocytic vacuoles (34) with lysosomes. This confines hydrolytic processes to the lysosome and presumably prevents unregulated intracellular digestion (13) .In various pathological states, cell injury may be produced by either extracellular or intracellular release of lysosomal enzymes (16). Extracellular release of lysosomal enzymes ac-

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confidence: 99%

“…In these cases, the late release of lysosomal enzymes simply accompanies lysis or enzymatic removal of dead cells. Numerous other examples of such a scavenging function of lysosomal enzyme release have been reviewed by Van Lanker (40) . Lysosomal rupture is temporally related to cell death in the toxicity of silica to macrophages (1,27).…”

mentioning

confidence: 99%

Dissociation of intracellular lysosomal rupture from the cell death caused by silica

Kane¹,

Stanton²,

Raymond³

et al. 1980

The Journal of Cell Biology

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“…However, a n increase in the activity of lysosomal hydrolases, proteinases among them, is known t o accompany cell death and tissue destruction or remodeling wherever they occur ( VAN LANCKER, 1970). Thus, higher proteinase activities may be a result of oligodendrocyte degeneration or of the ensuing response by surrounding astrocytes, rather than the initiating factor of myelin breakdown.…”

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confidence: 99%

A Thiol Proteinase Highly Elevated in and Around the Plaques of Multiple Sclerosis

Hirsch¹,

Parks²

1979

Journal of Neurochemistry

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Abstract— A thiol dependent proteolytic enzyme (tentatively identified as carboxypeptidase B) which liberates phenylalanine from CBZ‐glutamyl‐phenylalanine at pH 5.3 was shown, by a sensitive micromethod, to be greatly increased in activity in and around MS plaques. These increases exceeded those of other hydrolases previously measured. Plaque tissue, on the basis of lipid‐free dry weight, is up to 3‐fold richer in this enzyme than control white matter, and most samples of apparently uninvolved MS white matter already show elevated activities. The enzyme is highly dependent on the presence of dithiothreitol. It is unaffected by diisopropyl fluorophosphate and pepstatin, but inhibited by iodoacetate and leupeptin. Macrophages or lymphocytic infiltrations in the tissue do not appear to be the main source of the enzyme. In conjunction with measurements of DNA, reflecting gliosis, invasion by hematogenom cells and proliferation of phagocytes as well as oligodendrocyte loss, and acid lipase‐esterase, indicative of the survival or degeneration of oligodendrocytes, these results are interpreted as probably reflecting predominantly the activity of astrocytes. The incidental finding that most samples of unaffected white matter from MS patients contain more DNA per unit lipid free dry weight than average control white matter is considered significant in pointing to more widespread tissue changes independent of or preceding plaque formation.

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“…Hydrolases, however, were later shown to occur in association with the Golgi and/or Golgi-endoplasmic reticulum lysosomes, endoplasmic reticulum extracisternal spaces, and plasma membranes (for review see Bowen, 1981). In reference to inflammatory cells, it has been shown that acid hydrolases are directly transferred from the endoplasmic reticulum into foci of cytoplasmic degeneration (Van Lancker, 1975). It was later concluded that when cells die, areas of the cytoplasm become segregated for autolysis, and that these areas are supplied with hydrolases, either from primary lysosomes or directly from the endoplasmic reticulum.…”

Section: Protein Degradationmentioning

confidence: 99%

Current Concepts in Cell Death

Zhivotovsky

Orrenius

2001

CP Cell Biology

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This unit attempts to define cell toxicity that leads to cellular demise, with a strong emphasis on cell death via both apoptosis and necrosis, by summarizing some of the more recent developments in cellular, molecular, and biochemical studies of the events that govern the induction and execution of cell death. Specific topics pertaining to cell death include structural changes, macromolecular degradation, cellular signaling, the role of mitochondria, and genetic modulation of apoptotic cell death.

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Hydrolases and cellular death

Cited by 5 publications

References 16 publications

Dissociation of intracellular lysosomal rupture from the cell death caused by silica

Dissociation of intracellular lysosomal rupture from the cell death caused by silica

A Thiol Proteinase Highly Elevated in and Around the Plaques of Multiple Sclerosis

Current Concepts in Cell Death

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