Interaction of tomato lectin with ABC transporter in cancer cells: glycosylation confers functional conformation of P-gp.
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Interaction of tomato lectin with ABC transporter in cancer cells: glycosylation confers functional conformation of P-gp. / Molnár, Joseph; Kars, Meltem Demirel; Gündüz, Ufuk; Engi, Helga; Schumacher, Udo; Damme, Van; Els, J; Peumans, Willy J; Makovitzky, Josef; Gyémánt, Nóra; Molnár, Péter.
in: ACTA HISTOCHEM, Jahrgang 111, Nr. 4, 4, 2009, S. 329-333.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Interaction of tomato lectin with ABC transporter in cancer cells: glycosylation confers functional conformation of P-gp.
AU - Molnár, Joseph
AU - Kars, Meltem Demirel
AU - Gündüz, Ufuk
AU - Engi, Helga
AU - Schumacher, Udo
AU - Damme, Van
AU - Els, J
AU - Peumans, Willy J
AU - Makovitzky, Josef
AU - Gyémánt, Nóra
AU - Molnár, Péter
PY - 2009
Y1 - 2009
N2 - Phospho-glycoprotein (P-gp) is a polytopic plasma membrane protein whose overexpression causes multidrug resistance (MDR) responsible for the failure of cancer chemotherapy. P-gp 170 is a member of the ATP-binding cassette (ABC) transporter superfamily and has two potentially interesting regions for drugs interfering with its efflux function, namely the oligosaccharides on the first extracellular loop with unknown function and the two intracellular ATP-binding regions providing the energy for drug efflux function. The polylactoseamine oligosaccharides on the first loop can specifically bind the tomato lectin (TL). The P-gp efflux activities of TL-pre-treated MDR resistant cells were measured in the presence of structurally unrelated resistance modifiers such as phenothiazines, terpenoids and carotenoids. The inhibition of efflux activity was measured via the increased rhodamine uptake by mouse lymphoma cells transfected in human MDR1 gene and in human brain capillary endothelial cells. The tested resistance modifiers inhibit the function of ABC transporter resulting in increased R123 accumulation in MDR1 expressing cells. TL prevented the inhibitory action of phenothiazine and verapamil on brain capillary endothelial and MDR1-lymphoma cells, presumably due to the stabilization of the functional active conformation of P-gp. Our results indicate that the polylactosamine chains of P-gp are part of the functionally active protein conformation.
AB - Phospho-glycoprotein (P-gp) is a polytopic plasma membrane protein whose overexpression causes multidrug resistance (MDR) responsible for the failure of cancer chemotherapy. P-gp 170 is a member of the ATP-binding cassette (ABC) transporter superfamily and has two potentially interesting regions for drugs interfering with its efflux function, namely the oligosaccharides on the first extracellular loop with unknown function and the two intracellular ATP-binding regions providing the energy for drug efflux function. The polylactoseamine oligosaccharides on the first loop can specifically bind the tomato lectin (TL). The P-gp efflux activities of TL-pre-treated MDR resistant cells were measured in the presence of structurally unrelated resistance modifiers such as phenothiazines, terpenoids and carotenoids. The inhibition of efflux activity was measured via the increased rhodamine uptake by mouse lymphoma cells transfected in human MDR1 gene and in human brain capillary endothelial cells. The tested resistance modifiers inhibit the function of ABC transporter resulting in increased R123 accumulation in MDR1 expressing cells. TL prevented the inhibitory action of phenothiazine and verapamil on brain capillary endothelial and MDR1-lymphoma cells, presumably due to the stabilization of the functional active conformation of P-gp. Our results indicate that the polylactosamine chains of P-gp are part of the functionally active protein conformation.
M3 - SCORING: Zeitschriftenaufsatz
VL - 111
SP - 329
EP - 333
JO - ACTA HISTOCHEM
JF - ACTA HISTOCHEM
SN - 0065-1281
IS - 4
M1 - 4
ER -