Pitavastatin strengthens the barrier integrity in primary cultures of rat brain endothelial cells

Yoichi Morofuji, Shinsuke Nakagawa, Gohei So, Takeshi Hiu, Shoji Horai, Kentaro Hayashi, Kunihiko Tanaka, Kazuhiko Suyama, Maria A. Deli, Izumi Nagata, Masami Niwa

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)727-735
Number of pages9
JournalCellular and Molecular Neurobiology
Volume30
Issue number5
DOIs
Publication statusPublished - Jul 2010

Fingerprint

Endothelial Cells
Claudin-5
Blood-Brain Barrier
Electric Impedance
Brain
Tight Junction Proteins
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Mevalonic Acid
Tight Junctions
Terpenes
Neuroprotective Agents
Fluorescein
Permeability
Up-Regulation
Western Blotting
pitavastatin

Keywords

  • Blood-brain barrier
  • Brain endothelial cells (rat)
  • Claudin-5
  • Geranyl geranylation
  • Pitavastatin
  • Statins
  • Tight junctions
  • Transendothelial electrical resistance

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Pitavastatin strengthens the barrier integrity in primary cultures of rat brain endothelial cells. / Morofuji, Yoichi; Nakagawa, Shinsuke; So, Gohei; Hiu, Takeshi; Horai, Shoji; Hayashi, Kentaro; Tanaka, Kunihiko; Suyama, Kazuhiko; Deli, Maria A.; Nagata, Izumi; Niwa, Masami.

In: Cellular and Molecular Neurobiology, Vol. 30, No. 5, 07.2010, p. 727-735.

Research output: Contribution to journalArticle

Morofuji, Y, Nakagawa, S, So, G, Hiu, T, Horai, S, Hayashi, K, Tanaka, K, Suyama, K, Deli, MA, Nagata, I & Niwa, M 2010, 'Pitavastatin strengthens the barrier integrity in primary cultures of rat brain endothelial cells', Cellular and Molecular Neurobiology, vol. 30, no. 5, pp. 727-735. https://doi.org/10.1007/s10571-010-9497-9
Morofuji, Yoichi ; Nakagawa, Shinsuke ; So, Gohei ; Hiu, Takeshi ; Horai, Shoji ; Hayashi, Kentaro ; Tanaka, Kunihiko ; Suyama, Kazuhiko ; Deli, Maria A. ; Nagata, Izumi ; Niwa, Masami. / Pitavastatin strengthens the barrier integrity in primary cultures of rat brain endothelial cells. In: Cellular and Molecular Neurobiology. 2010 ; Vol. 30, No. 5. pp. 727-735.
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