Department of Neurology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, D-45122 Essen, Germany.
Sci Signal. 2010 Oct 5;3(142):ra72. doi: 10.1126/scisignal.2001213.
The adenosine triphosphate-binding cassette transporters ABCB1 and ABCC1 show coordinated changes in abundance at the luminal and abluminal membranes of ischemic cerebral capillaries that impede the brain access of pharmacological compounds. We found that apolipoprotein E (ApoE) was present on ischemic microvessels but not contralateral controls. ApoE signaled through ApoE receptor-2 (ApoER2), which was constitutively expressed on brain microvessels, to decrease c-Jun amino-terminal kinase 1 and 2 and c-Jun activities. ApoE regulated the postischemic abundance of ABCB1 and ABCC1, thereby controlling drug accumulation in the ischemic brain. Our data suggest that inhibition of ApoE signaling may enable improved delivery of drugs to the brain.
三磷酸腺苷结合盒转运蛋白 ABCB1 和 ABCC1 在缺血性脑毛细血管的腔膜和基底膜上的丰度呈协调变化，这阻碍了药理化合物进入大脑。我们发现载脂蛋白 E（ApoE）存在于缺血性微血管上，但在对侧对照中不存在。ApoE 通过在脑微血管上持续表达的载脂蛋白 E 受体-2（ApoER2）发出信号，以降低 c-Jun 氨基末端激酶 1 和 2 以及 c-Jun 的活性。ApoE 调节缺血后 ABCB1 和 ABCC1 的丰度，从而控制药物在缺血性大脑中的积累。我们的数据表明，抑制 ApoE 信号可能使药物更有效地递送到大脑。
