Transport of cycasin by the intestinal Na+/glucose cotransporter.
The medicinal and food use of seed from the cycad plant (Cycas spp.), which contains the neurotoxin cycasin, is a proposed etiological factor for amyotrophic lateral sclerosis/Parkinsonism dementia complex (ALS/PDC), a prototypical neurodegenerative disease found in the western Pacific. Cycasin, the beta-D-glucoside of methylazoxymethanol might enter neurons and other cells via a glucose transporter. Since the intestinal brush-border Na+/glucose cotransporter plays a major role in the absorption of monosaccharides, the following studies were conducted to determine if cycasin, the beta-D-glucoside of methylazoxymethanol, is a substrate for the transporter. We measured the ability of cycasin to (i) inhibit Na+/glucose uptake into rabbit intestinal brush-border membrane vesicles, and (ii) to generate current by the cloned Na+/glucose cotransporter (SGLT1) expressed in Xenopus laevis oocytes. The results show that cycasin inhibits Na(+)-dependent sugar transport in the vesicles, and cycasin generates phlorizin-sensitive currents in oocytes. We conclude that cycasin is a substrate for the intestinal brush-border Na+/glucose cotransporter, albeit with a lower affinity than D-glucose. This suggests that cycasin may be absorbed from the gut lumen by the cotransporter, and as a result either cycasin or the aglycone is presented to the blood-brain barrier for uptake into the brain.
Department of Physiology, UCLA School of Medicine.
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Hirayama
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Hazama
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Loo
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Wright
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Kisby
D000818:Animals; D001692:Biological Transport; D003492:Cycasin / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007672:Kidney Cortex / Q000378:metabolism; D008871:Microvilli / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D011817:Rabbits; D014981:Xenopus
D009004:Monosaccharide Transport Proteins; D003492:Cycasin