Cholesterol modulates P-glycoprotein activity in human peripheral blood mononuclear cells
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- 作者：Troost ; Joachim ; Albermann ; Nadine ; Emil Haefeli ; Walter ; Weiss ; Johanna
- 关键词：Cholesterol ; P-glycoprotein ; Cyclodextrins ; Rhodamine123 ; Membrane microdomains ; Caveolae ; Rafts ; Lymphocytes ; Monocytes
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2004
- 出版时间：April 9, 2004
- 年：2004
- 卷：316
- 期：3
- 页码：705-711
- 全文大小：700 K
文摘
P-glycoprotein (P-gp) is expressed in a wide range of cell types including peripheral blood mononuclear cells (PBMCs) where it may restrict intracellular accumulation of substrates like antineoplastic agents, HIV protease inhibitors, or rhodamine123. P-gp is known to be located in membrane microdomains, whose structure and function are susceptible to cholesterol alterations. This study evaluated the effect of cholesterol alteration in human PBMCs on P-gp activity. Whereas cholesterol depletion had no effect, cholesterol repletion of depleted cells significantly decreased intracellular rhodamine123 concentrations in lymphocytes to 32.2 % ±2.7 (p<0.001) and to 41.9 % ±3.5 (p<0.001) in monocytes. After cholesterol saturation of native cells intracellular rhodamine123 fluorescence decreased to 12.4 % ±1.6 (p<0.001) in lymphocytes and 12.9 % ±3.5 (p<0.001) in monocytes. These data demonstrate that elevated cellular cholesterol levels can markedly increase P-gp activity in human PBMCs.