Localization of organic cation/carnitine transporter (OCTN2) in cells forming the blood-brain barrier

被引:48
|
作者
Miecz, Dorota [1 ]
Januszewicz, Elzbieta [1 ]
Czeredys, Magdalena [1 ]
Hinton, Barry T. [2 ]
Berezowski, Vincent [3 ]
Cecchelli, Romeo [3 ]
Nalecz, Katarzyna A. [1 ]
机构
[1] M Nencki Inst Expt Biol, PL-02093 Warsaw, Poland
[2] Univ Virginia, Sch Med, Dept Cell Biol, Charlottesville, VA 22908 USA
[3] Univ Artois EA 2465, IMPRT IFR 114, Fac Sci Jean Perrin, Jean Perrin, Lens, France
关键词
astrocytes; blood-brain barrier; carnitine; organic cation/carnitine transporter 2;
D O I
10.1111/j.1471-4159.2007.05024.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Carnitine beta-hydroxy-gamma-(trimethylammonio)butyrate - a compound necessary in the peripheral tissues for a transfer of fatty acids for their oxidation within the cell, accumulates in the brain despite low beta-oxidation in this organ. In order to enter the brain, carnitine has to cross the blood-brain barrier formed by capillary endothelial cells which are in close interaction with astrocytes. Previous studies, demonstrating expression of mRNA coding two carnitine transporters - organic cation/carnitine transporter 2 (OCTN2) and B-0,B-+ in endothelial cells, did not give any information on carnitine transporters polarity in endothelium. Therefore more detailed experiments were performed on expression and localization of a high affinity carnitine transporter OCTN2 in an in vitro model of the blood-brain barrier by real-time PCR, western blot analysis, and immunocytochemistry. The amount of mRNA was comparable in endothelial cells and kidney, when referred to house-keeping genes, it was, however, significantly lower in astrocytes. Polarity of OCTN2 localization was further studied in an in vitro model of the blood-brain barrier with use of anti-OCTN2 antibodies. Z-axis analysis of the confocal microscope pictures of endothelial cells, with anti-P-glycoprotein antibodies as the marker of apical membrane, showed OCTN2 localization at the basolateral membrane and in the cytoplasmic region in the vicinity of nuclei. Localization of OCTN2 suggest that carnitine can be also transported from the brain, playing an important role in removal of certain acyl esters.
引用
收藏
页码:113 / 123
页数:11
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