title: Protective effects of vascular endothelial growth factor in cultured brain endothelial cells against hypoglycemia.
abstract: Hypoglycemia is a common and serious problem among patients with type 1 diabetes receiving treatment with insulin. Clinical studies have demonstrated that hypoglycemic edema is involved in the initiation of hypoglycemic brain damage. However, the mechanisms of this edema are poorly understood. Vascular endothelial growth factor (VEGF), a potent regulator of blood vessel function, has been observed an important candidate hormone induced by hypoglycemia to protect neurons by restoring plasma glucose. Whether VEGF has a protective effect against hypoglycemia-induced damage in brain endothelial cells is still unknown. To investigate the effects of hypoglycemia on cerebral microvascular endothelial cells and assess the protective effect of exogenous VEGF on endothelial cells during hypoglycemia, confluent monolayers of the brain endothelial cell line bEnd.3 were treated with normal (5.5 mM glucose), hypoglycemic (0, 0.5, 1 mM glucose) medium or hypoglycemic medium in the presence of VEGF. The results clearly showed that hypoglycemia significantly downregulated the expression of claudin-5 in bEnd.3 cells, without affecting ZO-1 and occludin expression and distribution. Besides, transendothelial permeability significantly increased under hypoglycemic conditions compared to that under control conditions. Moreover, the hypoglycemic medium in presence of VEGF decreased endothelial permeability via the inhibition of claudin-5 degradation and improved hypoglycemia-induced cell toxicity. Furthermore, Glucose transporter-1 (Glut-1) and apoptosis regulator Bcl-2 expression were significantly upregulated. Taken together, hypoglycemia can significantly increase paraendocellular permeability by downregulating claudin-5 expression. We further showed that VEGF protected brain endothelial cells against hypoglycemia by enhancing glucose passage, reducing endothelial cell death, and ameliorating paraendocellular permeability.
authors.affiliation: Neurologic Department, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No.600, Yishan Road, Xuhui District, Shanghai, 200233, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhao
authors.forename: Jiangshan
authors.initials: J
authors.lastname: Deng
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yu
authors.forename: Dawei
authors.initials: D
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Shi
authors.forename: Yuwu
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D007003:Hypoglycemia / Q000378:metabolism* / Q000517:prevention & control; D051379:Mice; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D020011:Protective Agents; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse