Lysosomal enzyme activities

In contradistinction to the decrease in lysosomal enzyme activity observed in alveolar macrophages and bronchial lavage fluid, Dillard et al. reported that continuous ozone exposure (0.70-0.79 ppm for 5-7 days) resulted in an increase in the activity of some lysosomal hydrolases in rat whole-lung homogenates and lung fractions, including the soluble supernatant. The tocopherol concentrations of the diet had no effect on the findings. 

In contrast to parasitic helminths, very few proteases of the snail hosts have been characterized at the functional and molecular levels (Sajid and McKerrow, 2002). Proteolytic enzymes have been implicated in playing a role in parasite destruction or survival in the snail host. Elevation of lysosomal enzyme activity in... 

Gold alters the morphology and functional capabilities of human macrophages—possibly its major mode of action. As a result, monocyte chemotactic factor-1, interleukin-8, interleukin-IB production, and vascular endothelial growth factor are all inhibited. Intramuscular gold compounds also alter lysosomal enzyme activity, reduce histamine release from mast cells, inactivate the first component of complement, and suppress the phagocytic activities of polymorphonuclear leukocytes. Auranofin also inhibits release of prostaglandin E2 and leukotriene B4. 

Beardall, C.H. and Johnston, I.A. (1985). Lysosomal enzyme activities in muscle following starvation and refeeding in the saithe Pollachius virens L.). European Journal of Cell Biology 39,112-117. 

B. Fisser-Szafriz and C. Nodal. Lysosomal enzyme activities in the regenerating int liver. Cancer Res. 37 354 (1977). 

Correct answer - C. Gold salts may not provide clinical improvement until after several weeks of administration. They are thought to suppress phagocytosis and lysosomal enzyme activity in macrophages. Gold salts are used in rheumatoid arthritis that does not respond to NSAIDs. Auranofin can be taken by mouth. 

By 6 months of age, psychomotor retardation is usually obvious. Joint immobility progresses with development of claw-hand deformities and kyphoscoliosis. Hepatomegaly is prominent, but splenomegaly is minimal. Corneal haziness may be present but is subtle, and corneal opacities due to the accumulation of storage material are not as striking as in Hurler syndrome. Examination of peripheral blood smears reveals the presence of abnormal inclusions in cells such as lymphocytes, and increased lysosomal enzyme activity in whole blood as well as cultured fibroblasts is confirmatory of I-cell disease. 

Biochemically, I-cell disease is characterized by excessive secretion of newly synthesized lysosomal enzymes into body fluids and concomitant loss of respective intracellular activities in fibroblasts. Shown in Table 17-1 are representative lysosomal enzyme activity levels in serum from patients with I-cell disease and those with the closely related disorder pseudo-Hurler poly dystrophy, indicating significantly increased levels of lysosomal enzyme activity. Germane to the biochemical diagnosis is the characteristic pattern of lysosomal enzyme deficiency in cultured fibroblasts, that is, an increase in the ratio of extracellular to intracellular enzyme activity (Table 17-2). It is interesting to note that not all lysosomal (i.e. intracellular)... 

Table 17-1. Lysosomal Enzyme Activities in Serum from Patients with I-Cell Disease and Pseudo-Hurler Polydystrophy ...

In this chapter, we indicate that the metabolic error (i.e., deficiency of phosphotransferase activity in I-cell disease) gives rise to a secondary phenotype of generalized diminished lysosomal enzyme activity. What other metabolic defects in the mannose 6-phosphate-mediated uptake system could result in such a phenotype, and how would you confirm the defect ... 

Weinreb, R.N., Jeng, S., and Miller, A.L., Lysosomal enzyme activity in human aqueous humor, Clin. Chim. Acta, 199, 1, 1991. 

Scherst4n, T., Wahlqvist, L., and Jilderos, B., Lysosomal enzyme activity in... 

Another important RPE function that might be altered by senescence, or by other stresses, is lysosomal enzyme actixfity. RPE cells digest the continuously growing outer segments (Sharma and Ehinger, 2003). A decrease in lysosomal enzyme activity has been reported to accompany the aging process. Impairment of RPE lysosomal enzymatic activity could play an important role in the development of AMD (Berson, 1973 Yamada et al. 1990 Boulton et al., 1994). Cathepsin D (CatD) is an aspartic protease lysosomal enzyme involved in opsin proteolysis. CatD is present in various retinal cell types, especially the RPE cells (Yamada et al., 1990). Its impairment could play a role in AMD. 

Ikemoto A. Fukuma A, Fujii Y, Okuyama H. Lysosomal enzyme activities are decreased in the retina but their circadian rhythms are maintained differently from those in the pineal gland in rats fed an a-linolenate-restricted diet. J Nutr 2000 130 3059-3062. 

Tissue damage present in RA is attributed in part to action of lytic lysosomal enzymes released by phagocytic cells in inflammed tissue. Auranofin inhibits the release of lysosomal enzymes from phagocytizing leukocytes at micromolar concentrations (1-10 uM) (44> 45). It did not produce leukocyte cytotoxicity nor inhibition of cell free lysosomal enzyme activity at these effective concentrations. Sodium aurothiomalate, aurothioglucose and odium aurothiosulfate did not exhibit this potent activity. 

Jung, S., Ghoul, M., and Lamballerie-Anton, M. De. 2000. Changes in lysosomal enzyme activities and shear values of high pressure treated meat during ageing. Meat Science 56 239-246. 

Shimomura, H., Takahashi, T., Morishita, T., and Ueno, R. 1987. Investigation of the differentiation of frozen-thawed fish from unfrozen fish by comparison of lysosomal enzyme activity. Nippon Suisan Gakkaishi 53 1841-1845. 

Salthouse TN, Matlaga BF, O Leary RK. 1973. Microspectrophotometry of macrophage lysosomal enzyme activity A measure of polymer implant tissue toxicity. Toxicol Appl Pharmacol 25 201-211. 

Fraser, J.R., Clarris, B.J., Baxter, E. 1979. Patterns of induced variation in the morphology, hyaluronic acid secretion, and lysosomal enzyme activity of cultured human synovial cells. Arm Rheum Dis 38(3), 287-294. 

Some recent investigations have failed to substantiate earlier claims that NAA are effective as a result of, helr ability to stabilize lysosome membranes. It has been concluded, however, that lysosome membrane stability is very much dependent on experimental conditions and that in vitro methods using rat liver lysosomes are not sufficient for studying the effect of antiinflammatory drugs. Increased lysosomal enzyme activity in homogenates of rat paws paralleled increases in paw volume in rats with adjuvant-induced arthritis. Oral administration of phenylbutazone arrested Increases in both enzyme activity and paw edema. Above normal lysozyme activity was found in the serum and synovial fluid of a signlficent proportion of patients with RA. ... 

Sylven. B. Lysosomal enzyme activity in the interstitial fluid of solid mouse tumor transplants. Eur. J. Cancer. 4 463-474.1968. Szent-Gydrgyi. A. Observations of the functions of peroxidase systems and the chemistry of the adrenal cortex. Biochem. J.. 22 1387-1409, 1928. 

Table 1. Lysosomal enzyme activities (nmol h" mg" protein) and sialic acid content. (From [25] with permission)...

Multiple lysosomal enzyme activities (secondary deficiencies) FB " CCV, AFC ... 

The same authors have also noticed important morphological differences in cultured peritoneal macrophages from High and Low responders, the latter, in addition, showed higher lysosomal enzyme activities. 

It is of interest that in adult rat skeletal muscle whose lysosomal enzyme activities were impaired by chloroquine treatment, AP was accumulated [177, 178]. Our newest studies demonstrated that inhibition of lysosomal activity in cultured human musde fibers induces in them AP oligomerization ([100], and below). 

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