Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Sci. Signal., 5 October 2010
Vol. 3, Issue 142, p. ra72
[DOI: 10.1126/scisignal.2001213]

RESEARCH ARTICLES

Apolipoprotein E Controls ATP-Binding Cassette Transporters in the Ischemic Brain

Ayman ElAli and Dirk M. Hermann*

Department of Neurology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, D-45122 Essen, Germany.

Abstract: 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.

* To whom correspondence should be addressed. E-mail: dirk.hermann{at}uk-essen.de

Citation: A. ElAli, D. M. Hermann, Apolipoprotein E Controls ATP-Binding Cassette Transporters in the Ischemic Brain. Sci. Signal. 3, ra72 (2010).

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Targeting blood-brain barrier sphingolipid signaling reduces basal P-glycoprotein activity and improves drug delivery to the brain.
R. E. Cannon, J. C. Peart, B. T. Hawkins, C. R. Campos, and D. S. Miller (2012)
PNAS 109, 15930-15935
   Abstract »    Full Text »    PDF »
The Abluminal Endothelial Membrane in Neurovascular Remodeling in Health and Disease.
D. M. Hermann and A. ElAli (2012)
Science Signaling 5, re4
   Abstract »    Full Text »    PDF »
Apolipoprotein-E Controls Adenosine Triphosphate-Binding Cassette Transporters ABCB1 and ABCC1 on Cerebral Microvessels After Methamphetamine Intoxication.
A. ElAli, A. Urrutia, A. Rubio-Araiz, M. Hernandez-Jimenez, M. I. Colado, T. R. Doeppner, and D. M. Hermann (2012)
Stroke 43, 1647-1653
   Abstract »    Full Text »    PDF »
Increased Blood-Brain Barrier Permeability and Brain Edema After Focal Cerebral Ischemia Induced by Hyperlipidemia: Role of Lipid Peroxidation and Calpain-1/2, Matrix Metalloproteinase-2/9, and RhoA Overactivation.
A. ElAli, T. R. Doeppner, A. Zechariah, and D. M. Hermann (2011)
Stroke 42, 3238-3244
   Abstract »    Full Text »    PDF »
ATP-Binding Cassette Transporters and Their Roles in Protecting the Brain.
A. ElAli and D. M. Hermann (2011)
Neuroscientist 17, 423-436
   Abstract »    PDF »
Science Signaling Podcast: 5 October 2010.
D. M. Hermann and A. M. VanHook (2010)
Science Signaling 3, pc18
   Abstract »    Full Text »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882