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Protective effects of vascular endothelial growth factor in cultured brain endothelial cells against hypoglycemia.

Zhao F, Deng J, Yu X, Li D, Shi H, Zhao Y - Metab Brain Dis (2015)

Bottom Line: Whether VEGF has a protective effect against hypoglycemia-induced damage in brain endothelial cells is still unknown.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.

View Article: PubMed Central - PubMed

Affiliation: Neurologic Department, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No.600, Yishan Road, Xuhui District, Shanghai, 200233, China.

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.

No MeSH data available.


Related in: MedlinePlus

Effects of hypoglycemia and VEGF treatment on cell viability. (a) Cells were maintained in 5.5 mM glucose (control) or 0, 0.5 and 1 mM glucose for the indicated times. The results are given as a percent relative to the control. (b) VEGF (100 ng/mL) was added to cultures at the onset of exposure to 0.5 and 5.5 mM (control) mM glucose medium for 24 h. Cell viability was determined by the LDH assay. Data are expressed as mean ± SEM. N = 3. *P < 0.05, **P < 0.01
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Fig5: Effects of hypoglycemia and VEGF treatment on cell viability. (a) Cells were maintained in 5.5 mM glucose (control) or 0, 0.5 and 1 mM glucose for the indicated times. The results are given as a percent relative to the control. (b) VEGF (100 ng/mL) was added to cultures at the onset of exposure to 0.5 and 5.5 mM (control) mM glucose medium for 24 h. Cell viability was determined by the LDH assay. Data are expressed as mean ± SEM. N = 3. *P < 0.05, **P < 0.01

Mentions: Endothelial cell death can augment BBB permeability (Engelhardt et al. 2014). Application of VEGF enhances cell survival and protects neurons against ischemic injury (Nishijima et al. 2007). We firstly assessed whether long-term hypoglycemia can induce bEnd.3 cell damage. Figure 5a showed that bEnd.3 cell viability decreased progressively after 24 h incubation with 0 and 0.5 mM glucose medium. To further examine the effect of VEGF on hypoglycemia-induced cell death, bEnd.3 cells were exposed to hypoglycemia in presence of VEGF (100 ng/ml). Figure 5b showed that a 24 h exposure to 0.5 mM glucose in presence of VEGF decreased cell death by 30.5 % compared with 0.5 mM glucose, suggesting the presence of VEGF significantly reduced cell death from hypoglycemia.Fig. 5


Protective effects of vascular endothelial growth factor in cultured brain endothelial cells against hypoglycemia.

Zhao F, Deng J, Yu X, Li D, Shi H, Zhao Y - Metab Brain Dis (2015)

Effects of hypoglycemia and VEGF treatment on cell viability. (a) Cells were maintained in 5.5 mM glucose (control) or 0, 0.5 and 1 mM glucose for the indicated times. The results are given as a percent relative to the control. (b) VEGF (100 ng/mL) was added to cultures at the onset of exposure to 0.5 and 5.5 mM (control) mM glucose medium for 24 h. Cell viability was determined by the LDH assay. Data are expressed as mean ± SEM. N = 3. *P < 0.05, **P < 0.01
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Fig5: Effects of hypoglycemia and VEGF treatment on cell viability. (a) Cells were maintained in 5.5 mM glucose (control) or 0, 0.5 and 1 mM glucose for the indicated times. The results are given as a percent relative to the control. (b) VEGF (100 ng/mL) was added to cultures at the onset of exposure to 0.5 and 5.5 mM (control) mM glucose medium for 24 h. Cell viability was determined by the LDH assay. Data are expressed as mean ± SEM. N = 3. *P < 0.05, **P < 0.01
Mentions: Endothelial cell death can augment BBB permeability (Engelhardt et al. 2014). Application of VEGF enhances cell survival and protects neurons against ischemic injury (Nishijima et al. 2007). We firstly assessed whether long-term hypoglycemia can induce bEnd.3 cell damage. Figure 5a showed that bEnd.3 cell viability decreased progressively after 24 h incubation with 0 and 0.5 mM glucose medium. To further examine the effect of VEGF on hypoglycemia-induced cell death, bEnd.3 cells were exposed to hypoglycemia in presence of VEGF (100 ng/ml). Figure 5b showed that a 24 h exposure to 0.5 mM glucose in presence of VEGF decreased cell death by 30.5 % compared with 0.5 mM glucose, suggesting the presence of VEGF significantly reduced cell death from hypoglycemia.Fig. 5

Bottom Line: Whether VEGF has a protective effect against hypoglycemia-induced damage in brain endothelial cells is still unknown.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.

View Article: PubMed Central - PubMed

Affiliation: Neurologic Department, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No.600, Yishan Road, Xuhui District, Shanghai, 200233, China.

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.

No MeSH data available.


Related in: MedlinePlus