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• W950666116 abstract "A P-glikoprotein (Pgp), a multidrog rezisztencia feherje 1 (MRP1) es az ABCG2 ABC transzporter feherjek membran kornyezete es transzport aktivitasa kozott oszzefuggest vizsgaltuk. Kiserleteink alapjan a sejtmembran raft regioiban talalhato Pgp-k ATP-hez valo affinitasa alacsony, igy a szubsztrat transzportban nem vesznek reszt, mig a raftokon kivul elhelyezkedő Pgp-k aktivan transzportalnak. Tehat a Pgp molekulak membran kornyezete meghatarozza funkcionalis allapotukat. Ko-immunprecipitacios kiserleteink alapjan a hsp71 es a miozin-9 a Pgp-vel es az ABCG2-vel is szorosan asszocialt. Jelenleg gencsendesitesi kiserletekben azt vizsgaljuk, hogy van-e ezen feherjeknek a transzporterek műkodesenek vagy sejtfelszini expressziojanak szabalyozasaban szerepe. A retinoidok, mint fiziologias szempontbol is jelentős lipofil molekulak, ABC transzporterekre kifejtett hatasat vizsgalva azt tapasztaltuk, hogy ezen transzporterek szeles szubsztrat spektrumuk ellenere erzekenyek a sztereokemiai kulonbsegekre. A Pgp katalitikus ciklusat vizsgalva megallapitottuk, hogy az ATP kotődese mindket ATP-kotőhelyhez elegseges ahhoz, hogy a Pgp molekulak atforduljanak a szubsztratkotő allapotbol az alacsony szubsztrat affinitasu allapotba. Bizonyitottuk, hogy a kis koncentracioban alkalmazott modulatorok es az UIC2 anti-Pgp antitest egyuttes adasa SCID egerekbe transzplantalt Pgp-t expresszalo multidrog rezisztens tumorok meretenek klinikailag is relevans mertekű csokkenesehez vezetett. | We have studied the correlation between transport characteristics and the membrane microenvironment of P-glycoprotein (Pgp), multidrug resistance protein 1 (MRP1) and ABCG2. We have demonstrated that the 20-40 % of Pgps are raft associated and found to be transport incompetent because of their low affinity to ATP and preferentially engaged in trafficking processes, while the non-raft Pgps are involved in substrate transport. Thus the membrane localization of Pgp molecules may determine their functional state. Based on our immunoprecipitation experiments hsp71 and myosin-9 are tightly associated with both Pgp and ABCG2. Since these proteins may potentially affect the expression or function of the examined transporters we are examining this issue by silencing them. Examining the effect of several physiologically relevant retinoids on the transport and ATPase activity of Pgp, ABCG2 and MRP1 we have found that stereo-chemical differences also affect the interactions between the retinoids and the transporters. We also demonstrated that the combined treatment with sub-inhibitory concentrations of Pgp modulators and UIC2 mAb can potentiate the anti-tumor effect of doxorubicin in Pgp+ tumors leading to clinically relevant reduction in tumor size. Studying the catalytic cycle of Pgp we have demonstrated that binding of ATP to both nucleotide binding domains is sufficient to switch Pgps from the high drug affinity conformation to the low drug affinity conformation." @default.
• W950666116 created "2016-06-24" @default.
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• W950666116 date "2013-01-01" @default.
• W950666116 modified "2023-09-24" @default.
• W950666116 title "A multidrog rezisztencia kialakulásában szerepet játszó ABC transzporterek membrán mikrokörnyezete = The membrane microenvironment of ABC transporters involved in multidrug resistance" @default.
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