Details

Autor(en) / Beteiligte

• Nan, Ding
• Jin, Haiqiang
• Deng, Jianwen
• Yu, Weiwei
• Liu, Ran
• Sun, Weiping
• Huang, Yining

Titel

Cilostazol ameliorates ischemia/reperfusion‐induced tight junction disruption in brain endothelial cells by inhibiting endoplasmic reticulum stress

Ist Teil von

• The FASEB journal, 2019-09, Vol.33 (9), p.10152-10164

Ort / Verlag

United States: Federation of American Societies for Experimental Biology

Erscheinungsjahr

2019

Quelle

Wiley Blackwell Single Titles

Beschreibungen/Notizen

• ABSTRACTEndoplasmic reticulum (ER) stress is essential for brain ischemia/reperfusion (I/R) injury. However, whether it contributes to I/R‐induced blood‐brain barrier (BBB) injury remains unclear, cilostazol exerts protective effects toward I/R‐induced BBB injury, with unclear mechanisms. This study explored the potential role of ER stress in I/R‐induced endothelial cell damage and determined whether the therapeutic potential of cilostazol, with respect to I/R‐induced endothelial cell damage, is related to inhibition of ER stress. We found that exposing brain endothelial cells (bEnd.3) to oxygen‐glucose deprivation/reoxygenation (OGD/R) significantly activated ER stress and diminished the barrier function of cell monolayers; treatment with the ER stress inhibitor 4‐phenylbutyric acid (4‐PBA) or cilostazol prevented OGD/R‐induced ER stress and preserved barrier function. Furthermore, OGD/R induced the expression and secretion of matrix metalloproteinase‐9 and nuclear translocation of phosphorylated NF‐κB. These changes were partially reversed by 4‐PBA or cilostazol treatment. In vivo, 4‐PBA or cilostazol significantly attenuated I/R‐induced ER stress and ameliorated Evans blue leakage and tight junction loss. These results demonstrate that I/R‐induced ER stress participates in BBB disruption. Targeting ER stress could be a useful strategy to protect the BBB from ischemic stroke, and cilostazol is a promising therapeutic agent for this process.—Nan, D., Jin, H., Deng, J., Yu, W., Liu, R., Sun, W., Huang, Y. Cilostazol ameliorates ischemia/reperfusion‐induced tight junction disruption in brain endothelial cells by inhibiting endoplasmic reticulum stress. FASEB J. 33,10152–10164 (2019). www.fasebj.org