scholarly journals Mutations in the facilitative glucose transporter GLUT10 alter angiogenesis and cause arterial tortuosity syndrome

2006 ◽  
Vol 38 (4) ◽  
pp. 452-457 ◽  
Author(s):  
Paul J Coucke ◽  
Andy Willaert ◽  
Marja W Wessels ◽  
Bert Callewaert ◽  
Nicoletta Zoppi ◽  
...  
Keyword(s):  
Glucose Transporter ◽  
Arterial Tortuosity ◽  
Arterial Tortuosity Syndrome ◽  
Facilitative Glucose Transporter

scholarly journals Slc2a10 knock-out mice deficient in ascorbic acid synthesis recapitulate aspects of arterial tortuosity syndrome and display mitochondrial respiration defects

2020 ◽  
Vol 29 (9) ◽  
pp. 1476-1488
Author(s):  
Annekatrien Boel ◽  
Joyce Burger ◽  
Marine Vanhomwegen ◽  
Aude Beyens ◽  
Marjolijn Renard ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Transforming Growth Factor Beta ◽  
Glucose Transporter ◽  
Transforming Growth Factor ◽  
Missense Mutations ◽  
Human Phenotype ◽  
Knock Out ◽  
Arterial Tortuosity ◽  
Arterial Tortuosity Syndrome ◽  
Knock Out Mice

Abstract Arterial tortuosity syndrome (ATS) is a recessively inherited connective tissue disorder, mainly characterized by tortuosity and aneurysm formation of the major arteries. ATS is caused by loss-of-function mutations in SLC2A10, encoding the facilitative glucose transporter GLUT10. Former studies implicated GLUT10 in the transport of dehydroascorbic acid, the oxidized form of ascorbic acid (AA). Mouse models carrying homozygous Slc2a10 missense mutations did not recapitulate the human phenotype. Since mice, in contrast to humans, are able to intracellularly synthesize AA, we generated a novel ATS mouse model, deficient for Slc2a10 as well as Gulo, which encodes for L-gulonolactone oxidase, an enzyme catalyzing the final step in AA biosynthesis in mouse. Gulo;Slc2a10 double knock-out mice showed mild phenotypic anomalies, which were absent in single knock-out controls. While Gulo;Slc2a10 double knock-out mice did not fully phenocopy human ATS, histological and immunocytochemical analysis revealed compromised extracellular matrix formation. Transforming growth factor beta signaling remained unaltered, while mitochondrial function was compromised in smooth muscle cells derived from Gulo;Slc2a10 double knock-out mice. Altogether, our data add evidence that ATS is an ascorbate compartmentalization disorder, but additional factors underlying the observed phenotype in humans remain to be determined.

scholarly journals Glucose transporter type 10-lacking in arterial tortuosity syndrome-facilitates dehydroascorbic acid transport

FEBS Letters ◽  
2016 ◽  
Vol 590 (11) ◽  
pp. 1630-1640 ◽  
Author(s):  
Csilla E. Németh ◽  
Paola Marcolongo ◽  
Alessandra Gamberucci ◽  
Rosella Fulceri ◽  
Angiolo Benedetti ◽  
...  
Keyword(s):  
Glucose Transporter ◽  
Dehydroascorbic Acid ◽  
Acid Transport ◽  
Arterial Tortuosity ◽  
Arterial Tortuosity Syndrome

scholarly journals SLC2A knockout mice deficient in ascorbic acid synthesis recapitulate aspects of arterial tortuosity syndrome and display mitochondrial respiration defects

2019 ◽  
Author(s):  
Annekatrien Boel ◽  
Joyce Burger ◽  
Marine Vanhomwegen ◽  
Aude Beyens ◽  
Marjolijn Renard ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Glucose Transporter ◽  
Dehydroascorbic Acid ◽  
Missense Mutations ◽  
Loss Of Function ◽  
Human Phenotype ◽  
Knock Out ◽  
Arterial Tortuosity ◽  
Arterial Tortuosity Syndrome ◽  
Knock Out Mice

AbstractArterial tortuosity syndrome (ATS) is a recessively inherited connective tissue disorder, mainly characterized by tortuosity and aneurysm formation of the major arteries. ATS is caused by loss-of-function mutations in SLC2A10, encoding the facilitative glucose transporter GLUT10. Former studies implicate GLUT10 in transport of dehydroascorbic acid, the oxidized form of ascorbic acid (AA). Mouse models carrying homozygous Slc2a10 missense mutations do not recapitulate the human phenotype. Since mice, in contrast to humans, are able to intracellularly synthesize AA, we generated a novel ATS mouse model, deficient for Slc2a10 as well as Gulo, which encodes for L-gulonolactone oxidase, an enzyme catalyzing the final step in AA biosynthesis in rodents. Gulo;Slc2a10 knock-out mice show mild phenotypic anomalies, which were absent in single knock-out controls. While Gulo;Slc2a10 knock-out mice do not fully phenocopy human ATS, histological and immunocytochemical analysis revealed compromised extracellular matrix formation. TGFβ signaling remained unaltered, while mitochondrial function was compromised in smooth muscle cells derived from Gulo;Slc2a10 knock-out mice. Altogether, our data add evidence that ATS is an ascorbate compartmentalization disorder, but additional factors underlying the observed phenotype in humans remain to be determined.

scholarly journals Low-dose CT angiography for evaluation of great vessels and airway in arterial tortuosity syndrome

2012 ◽  
Vol 13 (12) ◽  
pp. 1054-1054 ◽  
Author(s):  
M. Alkuwari ◽  
R. Y. Kamal ◽  
S. Shelby ◽  
S. T. Maliyekkal ◽  
S. Kutty
Keyword(s):  
Ct Angiography ◽  
Low Dose ◽  
Arterial Tortuosity ◽  
Low Dose Ct ◽  
Great Vessels ◽  
Arterial Tortuosity Syndrome

scholarly journals A possible role for a mammalian facilitative hexose transporter in the development of resistance to drugs.

1991 ◽  
Vol 11 (7) ◽  
pp. 3407-3418 ◽  
Author(s):  
J C Vera ◽  
G R Castillo ◽  
O M Rosen
Keyword(s):  
Xenopus Oocytes ◽  
Glucose Transporter ◽  
Cytochalasin B ◽  
Chinese Hamster ◽  
Multidrug Resistant ◽  
Xenopus Laevis Oocytes ◽  
Hexose Transporter ◽  
P Glycoprotein ◽  
Glut1 Protein ◽  
Facilitative Glucose Transporter

We show that D- but not L-hexoses modulate the accumulation of radioactive vinblastine in injected Xenopus laevis oocytes expressing the murine Mdr1b P-glycoprotein. We also show that X. laevis oocytes injected with RNA encoding the rat erythroid/brain glucose transport protein (GLUT1) and expressing the corresponding functional transporter exhibit a lower accumulation of [3H]vinblastine and show a greater capacity to extrude the drug than do control oocytes not expressing the rat GLUT1 protein. Cytochalasin B and phloretin, two inhibitors of the mammalian facilitative glucose transporters, can overcome the reduced drug accumulation conferred by expression of the rat GLUT1 protein in Xenopus oocytes but have no significant effect on the accumulation of drug by Xenopus oocytes expressing the mouse Mdr1b P-glycoprotein. These drugs also increase the accumulation of [3H]vinblastine in multidrug-resistant Chinese hamster ovary cells. Cytochalasin E, an analog of cytochalasin B that does not affect the activity of the facilitative glucose transporter, has no effect on the accumulation of vinblastine by multidrug-resistant Chinese hamster cells or by oocytes expressing either the mouse Mdr1b P-glycoprotein or the GLUT1 protein. In all three cases, the drug verapamil produces a profound effect on the cellular accumulation of vinblastine. Interestingly, although immunological analysis indicated the presence of massive amounts of P-glycoprotein in the multidrug-resistant cells, immunological and functional studies revealed only a minor increase in the expression of a hexose transporter-like protein in resistant versus drug-sensitive cells. Taken together, these results suggest the participation of the mammalian facilitative glucose transporter in the development of drug resistance.

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