Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The causation, structural origin, and mechanism of formation of spongiform lesions in transmissible encephalopathies are unknown. We have used immunogold electron microscopy to locate ubiquitin conjugates, hsp 70, and beta-glucuronidase (markers of the lysosomal compartment) and prion protein (PrP) in both control and scrapie-infected mouse brain. In scrapie-infected brain, lysosomes and lysosome-related structures (multivesicular and tubulovesicular dense bodies) are present in abnormally high numbers in neuronal cell processes. These structures contain PrP, together with the lysosomal markers ubiquitin conjugates, hsp 70, and beta-glucuronidase, which could also be identified spilling from tubulovesicular dense bodies into areas of early rarefaction in neuronal processes; we suggest that these areas of rarefaction are the precursor lesions of spongiform change. We advance the hypothesis that spongiform change is brought about by cytoskeletal disruption in neuronal processes caused by liberation of hydrolytic enzymes from lysosomes overloaded with the abnormal isoform of PrP (PrPsc). We suggest that the lysosomal system is probably acting as the bioreactor for processing of normal PrP to the abnormal isoform. The continuous production of increasing quantities of abnormal PrPsc in lysosome-related bodies will eventually cause disruption of the lysosomal membrane with destruction of the neuronal cytoskeleton and the initiation of vacuolation. Later, death of the cell will be associated with release of the PrPsc isoform into the extracellular environment. Repeated rounds of phagocytosis, lysosomal biogenesis of PrPsc, lysosomal membrane rupture, hydrolytic enzyme release, and neuronal lysis will lead to an exponential increase in cell damage and cell death.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lysosomes as key organelles in the pathogenesis of prion encephalopathies. 135 30

The effect of scrapie prion protein (PrP) either in the native or in the denatured form was studied on in vitro responses of human neutrophils. Incubation of neutrophils with native PrP caused an inhibition of their aggregation induced by cytochalasin B. Moreover, the denatured form was in itself a strong aggregation inducer. When evaluating the effect on generation of neutrophil superoxide anion (O2) we found that neutrophils released O2 in response to the denatured from only but the native form was ineffective. Similarly, neutrophil discharge of beta-glucuronidase which represents the azurophilic granule marker was stimulated in a dose-dependent form by the denatured PrP 27-30 whereas the native form was almost completely devoid of any activity. These results indicate that several aspects of neutrophil function can be altered by the native form of prion protein PrP 27-30. This might be responsible for the impaired phagocytic cell activity explaining, at least in part, the absence of any inflammatory reaction during scrapie infection.
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PMID:Inhibition of neutrophil functions by scrapie prion protein: description of some inhibitory properties. 198 77