Mécanismes de transport de glutathion : caractérisation et intervention lors de l'apoptose

Abstract : Our thesis work aims to study (1) the in vitro transport of glutathione in the endoplasmic reticulum (pig pancreas and rat liver) and (2) the transport of this tripeptide in MCF-7 and related cells from human mammary adenocarcinoma, when these cells are submitted to proapoptotic treatments. The intervention of the anti-apoptotic Bcl-2 protein in this last process has been evaluated. Rapid uItrafiltration was chosen to measure the transport activities of the microsomal tripeptide. Glutathione was quantified by high performance liquid chromatography. ln the first part of our work, we have observed a preferential uptake of reduced glutathione (GSH) only in RER microsomes, and a slow GSH efflux inhibited by anionic transporters inhibitors. The existence of a GSH transport mechanism involving the translocon in the \ endoplasmic reticulum is proposed. ln the second part of our work, we have shown that the overexpression of Bcl-2 in MCF-7 cells promotes cisplatin and adriamycine resistance by maintaining intracellular GSH level by an inhibition of GSH steady-state efflux. This work provides further insight into the anti-oxidant role ofBcl-2 in cells.
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Theses
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http://docnum.univ-lorraine.fr/prive/SCD_T_2006_0246_OSBILD.pdf
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https://hal.univ-lorraine.fr/tel-01747001
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Submitted on : Thursday, March 29, 2018 - 10:49:18 AM
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Sandra Osbild. Mécanismes de transport de glutathion : caractérisation et intervention lors de l'apoptose. Sciences agricoles. Université Henri Poincaré - Nancy 1, 2006. Français. ⟨NNT : 2006NAN10246⟩. ⟨tel-01747001⟩

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