Journal article
L‐Fucose Is a Potent Inhibitor of myo‐Inositol Transport and Metabolism in Cultured Neuroblastoma Cells
Journal of neurochemistry, Vol.58(5), pp.1626-1636
05/1992
DOI: 10.1111/j.1471-4159.1992.tb10034.x
PMID: 1313850
Abstract
: It has been proposed that abnormal myo‐inositol metabolism may be a factor in the development of diabetic complications. Studies with animal models of diabetes and cultured cells have suggested that hyperglycemia by an unknown mechanism may alter myo‐inositol metabolism and content. Recently, we have shown that L‐fucose, a 6‐deoxy sugar whose content has been reported to be increased in diabetes, is a potent inhibitor of myo‐inositol transport. To examine the effect of L‐fucose on myo‐inositol metabolism, neuroblastoma cells were cultured in medium supplemented with L‐fucose. L‐Fucose is a competitive inhibitor of Na+‐dependent, high‐affinity myo‐inositol transport. The Ki for inhibition of myo‐inositol transport by L‐fucose is about 3 mM. L‐Fucose is taken up and accumulates in neuroblastoma cells. The uptake of L‐fucose is inhibited by Na+ depletion, D‐glucose, glucose analogues, phloridzin, and cytochalasin B. In contrast, neither myo‐inositol nor L‐glucose inhibits L‐fucose uptake. Chronic exposure of neuroblastoma cells to 1–30 mM L‐fucose causes a decrease in myo‐inositol accumulation and incorporation into inositol phospholipids, intracellular free myo‐inositol content, and phosphatidylinositol levels. Na+,K+‐ATPase transport activity is decreased by about 15% by acute or chronic exposure of neuroblastoma cells to L‐fucose. Similar defects occur when neuroblastoma cells are exposed chronically to 30 mM glucose. Cell myo‐inositol metabolism and Na+/K+‐pump activity are maintained when 250 μM myo‐inositol is added to the L‐fucose‐supplemented medium. Unlike the effect of chronic exposure of neuroblastoma cells to medium containing 30 mM glucose, the resting membrane potential of neuroblastoma cells is not altered by chronic exposure of the cells to 30 mM L‐fucose. The effect of L‐fucose on cultured neuroblastoma cell properties occurs at concentrations of L‐fucose which may exist in the diabetic milieu. These data suggest that increased concentrations of L‐fucose may have a role in myo‐inositol‐related defects in mammalian cells.
Details
- Title: Subtitle
- L‐Fucose Is a Potent Inhibitor of myo‐Inositol Transport and Metabolism in Cultured Neuroblastoma Cells
- Creators
- Mark A YorekJoyce A DunlapMark R StefaniEric P Davidson
- Resource Type
- Journal article
- Publication Details
- Journal of neurochemistry, Vol.58(5), pp.1626-1636
- Publisher
- Blackwell Publishing Ltd
- DOI
- 10.1111/j.1471-4159.1992.tb10034.x
- PMID
- 1313850
- ISSN
- 0022-3042
- eISSN
- 1471-4159
- Number of pages
- 11
- Language
- English
- Date published
- 05/1992
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984094704302771
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