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Pitavastatin Strengthens the Barrier Integrity in Primary Cultures of Rat Brain Endothelial Cells.


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タイトル: Pitavastatin Strengthens the Barrier Integrity in Primary Cultures of Rat Brain Endothelial Cells.
著者: Morofuji, Yoichi / Nakagawa, Shinsuke / So, Gohei / Hiu, Takeshi / Horai, Shoji / Hayashi, Kentaro / Tanaka, Kunihiko / Suyama, Kazuhiko / Deli, Maria A / Nagata, Izumi / Niwa, Masami
発行日: 2010年 7月
出版者: Springer Netherlands
引用: Cellular and molecular neurobiology, 30(5), pp.727-735; 2010
抄録: 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.
キーワード: Blood-brain barrier / Brain endothelial cells (rat) / Claudin-5 / Geranyl geranylation / Pitavastatin / Statins / Tight junctions / Transendothelial electrical resistance
URI: http://hdl.handle.net/10069/23013
ISSN: 02724340
DOI: 10.1007/s10571-010-9497-9
PubMed ID: 20127168
権利: © Springer Science+Business Media, LLC 2010 / The original publication is available at www.springerlink.com
資料タイプ: Journal Article
原稿種類: author
出現コレクション:130 学術雑誌論文

引用URI : http://hdl.handle.net/10069/23013

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