Sac-1004, a novel vascular leakage blocker, enhances endothelial barrier through the cAMP/Rac/cortactin pathway

Sony Maharjan, Kyeojin Kim, Vijayendra Agrawal, Hyun Jung Choi, Nam Jung Kim, Young Myeong Kim, Young Ger Suh, Young-Guen Kwon

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The maintenance of endothelial barrier is critical for the vascular homeostasis and is maintained by the interaction of adherens junction (AJ) and tight junction (TJ) proteins between adjacent cells. This interaction is stabilized by actin cytoskeleton forming cortical actin ring. Here, we developed a novel vascular leakage blocker, Sac-1004 and investigated its mechanism of action in endothelial cells (ECs). Sac-1004 inhibited endothelial hyperpermeability induced by vascular endothelial growth factor, histamine and thrombin via stabilization of cortical actin ring and AJ proteins at the cell-cell junction. Treatment of Sac-1004 in ECs increased cAMP levels and activated Rac, both of which are known to strengthen endothelial barrier. Furthermore, Sac-1004 induced phosphorylation of cortactin and its localization at cell membrane that is essential for the stabilization of cortical actin ring. These effects of Sac-1004 on ECs were significantly abrogated by dideoxyadenosine (adenylyl cyclase inhibitor) and NSC23766 (Rac inhibitor). Taken together, our findings indicate that Sac-1004 blocks vascular leakage by enhancing endothelial integrity via the cAMP/Rac/cortactin pathway and imply the potential usefulness of Sac-1004 in the development of therapeutic means for vascular leakage-related diseases.

Original languageEnglish
Pages (from-to)420-427
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume435
Issue number3
DOIs
Publication statusPublished - 2013 Jun 7

Fingerprint

Cortactin
Blood Vessels
Actins
Endothelial cells
Adherens Junctions
Endothelial Cells
Stabilization
Dideoxyadenosine
Tight Junction Proteins
Phosphorylation
Cell membranes
Intercellular Junctions
Sac-1004
Adenylyl Cyclases
Thrombin
Histamine
Vascular Endothelial Growth Factor A
Actin Cytoskeleton
Homeostasis
Maintenance

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Maharjan, Sony ; Kim, Kyeojin ; Agrawal, Vijayendra ; Choi, Hyun Jung ; Kim, Nam Jung ; Kim, Young Myeong ; Suh, Young Ger ; Kwon, Young-Guen. / Sac-1004, a novel vascular leakage blocker, enhances endothelial barrier through the cAMP/Rac/cortactin pathway. In: Biochemical and Biophysical Research Communications. 2013 ; Vol. 435, No. 3. pp. 420-427.
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Sac-1004, a novel vascular leakage blocker, enhances endothelial barrier through the cAMP/Rac/cortactin pathway. / Maharjan, Sony; Kim, Kyeojin; Agrawal, Vijayendra; Choi, Hyun Jung; Kim, Nam Jung; Kim, Young Myeong; Suh, Young Ger; Kwon, Young-Guen.

In: Biochemical and Biophysical Research Communications, Vol. 435, No. 3, 07.06.2013, p. 420-427.

Research output: Contribution to journalArticle

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