?-Bungarotoxin impairs the vascular endothelial barrier function by inhibiting integrin a5

文献类型： 外文期刊

第一作者： Chen, Wei

作者： Chen, Wei;Liu, Wensen;Yu, Haotian;Sun, Chengbiao;Dong, Mingxin;Zhao, Na;Wang, Yan;Yu, Kaikai;Zhang, Jianxu;Liu, Wensen;Xu, Na

作者机构：

关键词： & gamma;-bungarotoxin; Disintegrins; Integrin & alpha;5; Vascular endothelium; Barrier

期刊名称：TOXICOLOGY LETTERS （ 影响因子：3.5； 五年影响因子：3.8 ）

ISSN： 0378-4274

年卷期： 2023 年 383 卷

页码：

收录情况： SCI

摘要： ?-bungarotoxin (?-BGT) is an RGD motif-containing protein, derived from the venom of Bungarus multicinctus, leading to acute death in mice. These RGD motif-containing proteins from snake venom belonging to the dis-integrin family can interfere with vascular endothelial homeostasis by directly binding cell surface integrins. Targeting integrins that generate vascular endothelial dysfunction may contribute to ?-BGT poisoning, however, the underlying mechanisms have not been investigated in detail. In this study, the results showed that ?-BGT played a role in-promoting the permeability of the vascular endothelial barrier. Depending on its selective binding to integrin a5 in vascular endothelium (VE), ?-BGT initiated downstream events, including focal adhesion kinase dephosphorylation and cytoskeleton remodeling, resulting in the intercellular junction inter-ruption. Those alternations facilitated paracellular permeability of VE and barrier dysfunction. Proteomics profiling identified that as a downstream effector of the integrin a5 / FAK signaling pathway cyclin D1 partially mediated the cellular structural changes and barrier dysfunction. Furthermore, VE-released plasminogen acti-vator urokinase and platelet-derived growth factor D could serve as potential diagnostic biomarkers for ?-BGT-induced vascular endothelial dysfunction. Our results indicate the mechanisms through which ?-BGT as a novel disintegrin directly interacts with the VE, with consequences for barrier dysfunction.

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