scholarly journals Glycogen storage disease type Ib: A defect in the glucose-6-phosphate transport system in microsomal membrane

1984 ◽  
Vol 29 (2) ◽  
pp. 77-87 ◽  
Author(s):  
Keiya Tada
Keyword(s):  
Transport System ◽  
Glycogen Storage Disease ◽  
Storage Disease ◽  
Glycogen Storage Disease Type ◽  
Phosphate Transport ◽  
Glycogen Storage ◽  
Disease Type ◽  
Microsomal Membrane

Inhibition of microsomal glucose-6-phosphate transport in human neutrophils results in apoptosis: a potential explanation for neutrophil dysfunction in glycogen storage disease type 1b

Blood ◽  
2003 ◽  
Vol 101 (6) ◽  
pp. 2381-2387 ◽  
Author(s):  
Rosanna Leuzzi ◽  
Gábor Bánhegyi ◽  
Tamás Kardon ◽  
Paola Marcolongo ◽  
Piero-Leopoldo Capecchi ◽  
...  
Keyword(s):  
Glycogen Storage Disease ◽  
Storage Disease ◽  
Glycogen Storage Disease Type ◽  
Phosphate Transport ◽  
Glycogen Storage ◽  
Disease Type ◽  
Jurkat Cells ◽  
Phosphate Transporter ◽  
Disulfonic Acid ◽  
Human Neutrophils

Mutations in the gene of the hepatic glucose-6-phosphate transporter cause glycogen storage disease type 1b. In this disease, the altered glucose homeostasis and liver functions are accompanied by an impairment of neutrophils/monocytes. However, neither the existence of a microsomal glucose-6-phosphate transport, nor the connection between its defect and cell dysfunction has been demonstrated in neutrophils/monocytes. In this study we have characterized the microsomal glucose-6-phosphate transport of human neutrophils and differentiated HL-60 cells. The transport of glucose-6-phosphate was sensitive to the chlorogenic acid derivative S3483,N-ethylmaleimide, and 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid, known inhibitors of the hepatic microsomal glucose-6-phosphate transporter. A glucose-6-phosphate uptake was also present in microsomes from undifferentiated HL-60 and Jurkat cells, but it was insensitive to S3483. The treatment with S3484 of intact human neutrophils and differentiated HL-60 cells mimicked some leukocyte defects of glycogen storage disease type 1b patients (ie, the drug inhibited phorbol myristate acetate–induced superoxide anion production and reduced the size of endoplasmic reticulum Ca2+ stores). Importantly, the treatment with S3484 also resulted in apoptosis of human neutrophils and differentiated HL-60 cells, while undifferentiated HL-60 and Jurkat cells were unaffected by the drug. The proapoptotic effect of S3483 was prevented by the inhibition of nicotinamide adenine dinucleotide phosphate oxidase or by antioxidant treatment. These results suggest that microsomal glucose-6-phosphate transport has a role in the antioxidant protection of neutrophils, and that the genetic defect of the transporter leads to the impairment of cellular functions and apoptosis.

Glucose 6-phosphate transport in fibroblast microsomes from glycogen storage disease type 1b patients: evidence for multiple glucose 6-phosphate transport systems

2001 ◽  
Vol 357 (2) ◽  
pp. 557-562 ◽  
Author(s):  
Rosanna LEUZZI ◽  
Rosella FULCERI ◽  
Paola MARCOLONGO ◽  
Gábor BÁNHEGYI ◽  
Enrico ZAMMARCHI ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Phosphatase Activity ◽  
Glycogen Storage Disease ◽  
Storage Disease ◽  
Glycogen Storage Disease Type ◽  
Phosphate Transport ◽  
Glycogen Storage ◽  
Disease Type ◽  
Transport Systems ◽  
Transport Activity

In liver endoplasmic reticulum the intralumenal glucose-6-phosphatase activity requires the operation of a glucose 6-phosphate transporter (G6PT1). Mutations in the gene encoding G6PT1 cause glycogen storage disease type 1b, which is characterized by a loss of glucose-6-phosphatase activity and impaired glucose homoeostasis. We describe a novel glucose 6-phosphate (G6P) transport activity in microsomes from human fibroblasts and HeLa cells. This transport activity is unrelated to G6PT1 since: (i) it was similar in microsomes of skin fibroblasts from glycogen storage disease type 1b patients homozygous for mutations of the G6PT1 gene, and in microsomes from human control subjects; (ii) it was insensitive to the G6PT1 inhibitor chlorogenic acid; and (iii) it was equally active towards G6P and glucose 1-phosphate, whereas G6PT1 is highly selective for G6P. Taken together, our results provide evidence for the presence of multiple transporters for G6P (and other hexose phosphoesters) in the endoplasmic reticulum.

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