Influence of glutathione depletion on plasma membrane cholesterol esterification and on Tc-99m-sestamibi and Tc-99m-tetrofosmin uptakes : a comparative study in sensitive U-87-MG and multidrug-resistant MRP1 human glioma cells

In our previous studies, we demonstrated a possible effect of cellular glutathione (GSH) depletion on plasma-membrane permeability and fluidity in glioma-cell lines. We therefore investigated the effect of GSH modulation on accumulation of two radiotracers, Tc-99m-sestamibi (MIBI) and Tc-99m-tetrofosmin (TFOS), and on plasma-membrane cholesterol content in sensitive U-87-MG and resistant U-87-MG-CIS and U-87-MG-MEL (MRP1 positive) human glioma-cell lines. GSH depletion was mediated by BSO pretreatment and addition of N-acetylcysteine reversed the effect. MIBI and TFOS uptakes, total cholesterol, and cholesteryl-ester contents were evaluated under each condition. In contrast with TFOS, MIBI accumulation was inversely proportional to the cell multidrug resistance phenotype. Similar cholesterol contents were observed in all cell lines, demonstrating that MRP1 did not modify lipid membrane composition. A decrease of intracellular GSH allows an increase of plasma-membrane cholesterol and a decrease of choleste...