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

被引:25
作者
Le Jeune, N
Perek, N
Denoyer, D
Dubois, F
机构
[1] Fac Med, Lab Biophys, F-42023 St Etienne 02, France
[2] Fac Med, Lab Biophys Res Grp EA 3063 Cellular Survival & A, F-42023 St Etienne 02, France
关键词
MRP1; cholesterol; malignant glioma; Tc-99m-tetrofosmin (TFOS); Tc-99m-sestamibi (MIBI); glutathione (GSH);
D O I
10.1089/cbr.2004.19.411
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 cholesteryl-ester content, which in turn results in spectacular TFOS uptake. The GSH status of the cells plays an important role in the plasma membrane cholesterol composition and TFOS uptake, which appears to be particularly sensitive to this modification. In contrast with MIBI, TFOS is not an MRP1 probe in glioma cells, and therefore appears to be a suitable tracer in this indication.
引用
收藏
页码:411 / 421
页数:11
相关论文
共 37 条
[1]   Expression of multidrug resistance protein gene in patients with glioma after chemotherapy [J].
Abe, T ;
Mori, T ;
Wakabayashi, Y ;
Nakagawa, M ;
Cole, SPC ;
Koike, K ;
Kuwano, M ;
Hori, S .
JOURNAL OF NEURO-ONCOLOGY, 1998, 40 (01) :11-18
[2]   TC-99(M)-SESTAMIBI AS AN AGENT FOR IMAGING P-GLYCOPROTEIN-MEDIATED MULTIDRUG-RESISTANCE - IN-VITRO AND IN-VIVO STUDIES IN A RAT BREAST-TUMOR CELL-LINE AND ITS DOXORUBICIN-RESISTANT VARIANT [J].
BALLINGER, JR ;
HUA, HA ;
BERRY, BW ;
FIRBY, P ;
BOXEN, I .
NUCLEAR MEDICINE COMMUNICATIONS, 1995, 16 (04) :253-257
[3]   The multidrug resistance protein family [J].
Borst, P ;
Evers, R ;
Kool, M ;
Wijnholds, J .
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 1999, 1461 (02) :347-357
[4]   ABC transporters in lipid transport [J].
Borst, P ;
Zelcer, N ;
van Helvoort, A .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 2000, 1486 (01) :128-144
[5]  
Campanella R, 1992, J Neurosurg Sci, V36, P11
[6]   Brain tumor imaging with 99mTc-tetrofosmin:: comparison with 201Tl, 99mTc-MIBI, and 18F-fluorodeoxyglucose [J].
Choi, JY ;
Kim, SE ;
Shin, HJ ;
Kim, BT ;
Kim, JH .
JOURNAL OF NEURO-ONCOLOGY, 2000, 46 (01) :63-70
[7]  
Cole SPC, 1998, BIOESSAYS, V20, P931, DOI 10.1002/(SICI)1521-1878(199811)20:11<931::AID-BIES8>3.0.CO
[8]  
2-J
[9]  
Cordobes MD, 1996, J NUCL MED, V37, P286
[10]   POTENTIATION OF ANTICANCER-DRUG CYTOTOXICITY BY MULTIDRUG-RESISTANCE CHEMOSENSITIZERS INVOLVES ALTERATIONS IN MEMBRANE FLUIDITY LEADING TO INCREASED MEMBRANE-PERMEABILITY [J].
DRORI, S ;
EYTAN, GD ;
ASSARAF, YG .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1995, 228 (03) :1020-1029