The effect of glibenclamide in lipopolysaccharide stimulated brain microvascular endothelial cells
tarafından
Cihankaya, Hilal, author.
Başlık
:
The effect of glibenclamide in lipopolysaccharide stimulated brain microvascular endothelial cells
Yazar
:
Cihankaya, Hilal, author.
Yazar Ek Girişi
:
Cihankaya, Hilal, author.
Fiziksel Tanımlama
:
xi, 44 leaves: charts;+ 1 computer laser optical disc
Özet
:
Endothelial cells are essential components of the blood brain barrier (BBB) that regulate the exchange of solutes between the vasculature and the brain parenchyma. The integrity of the BBB is disrupted after central nervous system (CNS) injuries, and it has been associated with the Sur1-Trpm4 channels. Once these channels are opened, Na+ flows into the cells causing edema and cell death. To mimic CNS injuries in vitro, lipopolysaccharide (LPS) was used as an endotoxin to initiate proinflammatory mediators to increase endothelial permeability, and glibenclamide was used as an antagonist of Sur1-Trpm4 channels to reduce the inflammatory response and to maintain the structural integrity of BBB proteins. To demonstrate the role of glibenclamide following LPS stimulation, we determined the cytotoxicity of LPS in bEnd.3 cells by cleaved caspase-3 expression and propidium iodide staining. We also investigated the protective effect of glibenclamide on NF-B translocation, and BBB proteins; collagen IV (COL IV) and zonula occludens 1 (ZO-1) in LPS stimulated bEnd.3 cells. Our results revealed that 1g/ml LPS exposure was sufficient for NF-B nuclear translocation, along with a statistically significant decrease in the expressions of COL IV and ZO-1 proteins, and a significant increase in cell death. We also demonstrated that glibenclamide was able to restore the expressions of COL IV and ZO-1, significantly reduce NF-B translocation, and cell death. Taken together, LPS induction in bEnd.3 cells can be used to investigate endothelial cell dysfunction due to inflammation in stroke and trauma models and glibenclamide can be used as a protective drug to inhibit LPS stimulated inflammatory response, cell death and disruptions in the structures of key BBB proteins. Keywords: brain microvascular endothelial cells, lipopolysaccharide, glibenclamide, Sur1-Trpm4 channel
Konu Başlığı
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Blood-brain barrier.
Endotoxins.
Endothelial cells.
Glibenclamide.
Microcirculation.
Yazar Ek Girişi
:
Tosun, Çiğdem,
Tüzel Kişi Ek Girişi
:
İzmir Institute of Technology. Molecular Biology and Genetics.
Tek Biçim Eser Adı
:
Thesis (Master)--İzmir Institute of Technology: Molecular Biology and Genetics.
İzmir Institute of Technology: Molecular Biology and Genetics.--Thesis (Master).
Elektronik Erişim
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Library | Materyal Türü | Demirbaş Numarası | Yer Numarası | Durumu/İade Tarihi |
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IYTE Library | Tez | T001974 | QP375.5 .C571 2019 | Tez Koleksiyonu |