RT Journal Article
SR Electronic
T1 Apolipoprotein E Controls ATP-Binding Cassette Transporters in the Ischemic Brain
JF Science Signaling
JO Sci. Signal.
FD American Association for the Advancement of Science
SP ra72
OP ra72
DO 10.1126/scisignal.2001213
VO 3
IS 142
A1 ElAli, Ayman
A1 Hermann, Dirk M.
YR 2010
UL http://stke.sciencemag.org/content/3/142/ra72.abstract
AB 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.