Pitavastatin strengthens the barrier integrity in primary cultures of rat brain endothelial cells.
Statins have a neuroprotective effect in neurological diseases, a pleiotropic effect possibly related to blood-brain barrier (BBB) function. We investigated the effect of pitavastatin on barrier functions of an in vitro BBB model with primary cultures of rat brain capillary endothelial cells (RBEC). Pitavastatin increased the transendothelial electrical resistance (TEER), an index of barrier tightness of interendothelial tight junctions (TJs), at a concentration of 10(-8) M, and decreased the endothelial permeability for sodium fluorescein through the RBEC monolayer. The increase in TEER was significantly reduced in the presence of isoprenoid geranylgeranyl pyrophosphate, whereas farnesyl pyrophosphate had no effect on TEER. Our immunocytochemical and Western blot analyses revealed that treatment with pitavastatin enhanced the expression of claudin-5, a main functional protein of TJs. Our data indicate that pitavastatin strengthens the barrier integrity in primary cultures of RBEC. The BBB-stabilizing effect of pitavastatin may be mediated partly through inhibition of the mevalonate pathway and subsequent up-regulation of claudin-5 expression.
Morofuji
Yoichi
Y
Department of Neurosurgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. nounaga2009@gmail.com
Nakagawa
Shinsuke
S
So
Gohei
G
Hiu
Takeshi
T
Horai
Shoji
S
Hayashi
Kentaro
K
Tanaka
Kunihiko
K
Suyama
Kazuhiko
K
Deli
Maria A
MA
Nagata
Izumi
I
Niwa
Masami
M
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D001921:Brain / Q000166:cytology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D057167:Claudins / Q000235:genetics / Q000378:metabolism; D017097:Electric Impedance; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects; D011106:Polyisoprenyl Phosphates / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012717:Sesquiterpenes / Q000494:pharmacology; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism
D015415:Biomarkers; D057167:Claudins; D011106:Polyisoprenyl Phosphates; D011804:Quinolines; D012333:RNA, Messenger; D012717:Sesquiterpenes; C004808:farnesyl pyrophosphate; C108475:pitavastatin; C002963:geranylgeranyl pyrophosphate