Subcellular Fractionation Studies on Hepatic Tissue from a Patient with Pompe's Disease (Type II Glycogen-Storage Disease)

Peters, T J; Jenkins, W. J.; Dubowitz, Victor

doi:10.1042/cs0590007

Cited by 7 publications

(3 citation statements)

References 23 publications

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“…In contrast, other investigators report the presence of membrane fragments in relation to the cytoplasmic glycogen stores and suggest that these glycogen accumulations result from rupture of distended glycogen-filled vacuoles (Martin et al, 1973;Engel et aI., 1973;Hudgson and Fulthorpe, 1975;Gultotta et aI., 1976;Griffin, 1984). Enhanced lysosomal fragility has been described in human GSD II (Peters et al, 1980). Our ultrastructural findings support this hypothesis of vacuolar rupture.…”

Section: Ultrastructural Pathologysupporting

confidence: 89%

Comparative pathology of the canine model of glycogen storage disease type II (Pompe's disease)

Walvoort

Dormans

Ingh

1984

J of Inher Metab Disea

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The pathology of canine glycogen storage disease type II (acid alpha-glucosidase deficiency, GSD II) was studied in three genetically related Lapland dogs and compared to the pathology of human GSD II (McKusick 23230). Canine GSD II closely parallels the infantile form of the human disease, except for the presence of oesophageal dilatation. Generalized glycogen storage particularly affected muscular tissues (skeletal, oesophageal, cardiac and smooth muscle). The altered cells showed glycogen accumulation in the cytosol and in autophagic membrane-bound vacuoles (glycogenosomes). They also showed increased acid phosphatase activity consistent with the lysosomal nature of this storage disorder. The cytopathology in canine and human GSD II appears to evolve from segregation of glycogen during regular cellular autophagy, phagolysosomal accumulation of the undigested glycogen, and eventually rupture of distended glycogenosomes. This study indicates that the usefulness of canine GSD II as an animal model of human disease, extends to the area of pathogenesis.

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Section: Ultrastructural Pathologysupporting

confidence: 89%

Comparative pathology of the canine model of glycogen storage disease type II (Pompe's disease)

Walvoort

Dormans

Ingh

1984

J of Inher Metab Disea

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“…However, in studies using acarbose, no enzymatic activities were measured, and no correlations between glycogen levels or distribution and aglucosidase activity could be drawn. It may be of interest that individuals with type II glycogenosis frequently have an elevation in the activity of P-N-acetylhexosaminidase of liver (10). In livers of animals treated with castanospermine, this enzymatic activity was also elevated.…”

Section: Resultsmentioning

confidence: 98%

Castanospermine inhibits alpha-glucosidase activities and alters glycogen distribution in animals.

Saul¹,

Ghidoni²,

Molyneux³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

126

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Castanospermine, an inhibitor of a-glucosidase activity, was injected into rats to determine its effects in vivo. Daily injections of alkaloid, at levels of 0.5 mg/g of body weight, or higher, for 3 days decreased hepatic a-glucosidase to 40% of control values, whereas a-glucosidase in brain was reduced to 25% of control values and that in spleen and kidney was reduced to about 40%. In liver, both the neutral (pH 6.5) and the acidic (pH 4.5) a-glucosidase activities were inhibited, but the former was more susceptible. On the other hand, 13-Nacetylhexosaminidase activity was elevated in the livers of treated animals, whereas f8-galactosidase activity was unchanged and a-mannosidase activity was somewhat inhibited. Livers of treated animals were examined by light and electron microscopy and compared to control animals to determine whether changes in morphology had occurred. In treated animals fed normal rat chow, the hepatocytes were smaller in size and simplified in structure, whereas the high-glucose diet lessened these alterations. Furthermore, in those animals receiving castanospermine at 1.0 mg or higher per g of body weight for 3 days, there was a marked decrease in the amount of glycogen in the cytoplasm, while a large number of lysosomes were observed that were full of dense, granular material. That this dense material was indeed glycogen was shown by the fact that it disappeared when blocks of fixed tissue were pretreated with a-amylase. Glycogen levels in liver, as measured either colorimetrically or enzymatically, were somewhat depressed at the higher levels of castanospermine.Castanospermine (1,6,7,8-tetrahydroxyoctahydroindolizine) is an indolizine alkaloid that is found in the seeds of the Australian tree Castanospermum australe (1). These seeds have been reported to be toxic to animals and to cause various symptoms, including gastrointestinal upset. We recently found that this alkaloid was a potent inhibitor of lysosomal a-and ,3-glucosidase but had no effect on a number of other glycosidases (2). In addition, castanospermine also inhibits the neutral glucosidase(s) that participates in the processing of the oligosaccharide chains of the N-linked glycoproteins (3). Thus, in cultured mammalian cells, castanospermine prevents the formation of complex chains and gives rise to glycoproteins having mostly Glc3Man7_9GlcNAc2 structures.Since glucosidases are very important enzymes in a number of metabolic sequences, including glycogen degradation, we were interested in determining whether this alkaloid would affect glycogen metabolism if injected into animals. Based on preliminary experiments, we postulated that castanospermine would inhibit the lysosomal a-glucosidase and produce a lysosomal block leading to the abnormal storage of glycogen. The data presented in this paper show that this alkaloid markedly depressed the activity levels of a-glucosidase in liver and other tissues. Coupled with this decreased activity was the finding that the livers of rats given this alkaloid for several days had...

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“…Chemical and enzymic procedures (Na+ + K+)-dependent ATPase (EC 3.6.1.3), succinate dehydrogenase (EC 1.3.99.1), acetylcholinesterase (EC 3.1.1.7) and neutral a-Dglucosidase (EC 3.2.1.20) activities were determined as described previously (Ellman et al, 1961;Earl & Korner, 1965;Verity, 1972;Peters et al, 1980). Samples for lactate dehydrogenase (EC 1.1.1.27) were assayed in the presence of 0.05% Triton X-l00 (Johnson, 1960).…”

Section: Incubation With Na235so4mentioning

confidence: 99%

The incorporation in vitro of sulphate ions into synaptic-membrane glycoproteins

Ltd¹

1982

Biochemical Journal

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Subcellular Fractionation Studies on Hepatic Tissue from a Patient with Pompe's Disease (Type II Glycogen-Storage Disease)

Cited by 7 publications

References 23 publications

Comparative pathology of the canine model of glycogen storage disease type II (Pompe's disease)

Comparative pathology of the canine model of glycogen storage disease type II (Pompe's disease)

Castanospermine inhibits alpha-glucosidase activities and alters glycogen distribution in animals.

The incorporation in vitro of sulphate ions into synaptic-membrane glycoproteins

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