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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 VEGF on hypoglycemia-induced paracellular permeability and TJ proteins. (a) Effect of VEGF (100 ng/ml) on cell permeability of cells exposed to 0.5 and 5.5 mM glucose for 24 h. (b) Effects of VEGF on TJ protein levels during hypoglycemia for 24 h in bEnd.3 cells. Representative TJ Western blots are shown following treatment with 0.5 or 5.5 mM glucose for 24 h with the presence of 100 ng/ml VEGF. Summary plots of claudin-5 (c), occludin (d), and ZO-1 (e) are shown following densitometric analysis of the corresponding protein blots. Data are expressed as the mean ± SEM. N = 3. *P < 0.05, **P < 0.01
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Fig4: Effects of VEGF on hypoglycemia-induced paracellular permeability and TJ proteins. (a) Effect of VEGF (100 ng/ml) on cell permeability of cells exposed to 0.5 and 5.5 mM glucose for 24 h. (b) Effects of VEGF on TJ protein levels during hypoglycemia for 24 h in bEnd.3 cells. Representative TJ Western blots are shown following treatment with 0.5 or 5.5 mM glucose for 24 h with the presence of 100 ng/ml VEGF. Summary plots of claudin-5 (c), occludin (d), and ZO-1 (e) are shown following densitometric analysis of the corresponding protein blots. Data are expressed as the mean ± SEM. N = 3. *P < 0.05, **P < 0.01

Mentions: Since TJ-mediated regulation of endothelial permeability is vital to BBB integrity, we assessed the effect of exogenous VEGF (100 ng/ml) on permeability in bEnd.3 cells under hypoglycemic conditions by measuring the ability of Na-F to cross the cell monolayer 24 h after 0.5 mM glucose treatment. As shown in Fig. 4a, a 24 h exposure to 0.5 mM glucose in presence of VEGF decreased the Na-F permeability by 30.8 % compared with 0.5 mM glucose, suggesting the presence of VEGF significantly decreased the enhanced endothelial permeability caused by hypoglycemia.Fig. 4


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 VEGF on hypoglycemia-induced paracellular permeability and TJ proteins. (a) Effect of VEGF (100 ng/ml) on cell permeability of cells exposed to 0.5 and 5.5 mM glucose for 24 h. (b) Effects of VEGF on TJ protein levels during hypoglycemia for 24 h in bEnd.3 cells. Representative TJ Western blots are shown following treatment with 0.5 or 5.5 mM glucose for 24 h with the presence of 100 ng/ml VEGF. Summary plots of claudin-5 (c), occludin (d), and ZO-1 (e) are shown following densitometric analysis of the corresponding protein blots. Data are expressed as the mean ± SEM. N = 3. *P < 0.05, **P < 0.01
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4491374&req=5

Fig4: Effects of VEGF on hypoglycemia-induced paracellular permeability and TJ proteins. (a) Effect of VEGF (100 ng/ml) on cell permeability of cells exposed to 0.5 and 5.5 mM glucose for 24 h. (b) Effects of VEGF on TJ protein levels during hypoglycemia for 24 h in bEnd.3 cells. Representative TJ Western blots are shown following treatment with 0.5 or 5.5 mM glucose for 24 h with the presence of 100 ng/ml VEGF. Summary plots of claudin-5 (c), occludin (d), and ZO-1 (e) are shown following densitometric analysis of the corresponding protein blots. Data are expressed as the mean ± SEM. N = 3. *P < 0.05, **P < 0.01
Mentions: Since TJ-mediated regulation of endothelial permeability is vital to BBB integrity, we assessed the effect of exogenous VEGF (100 ng/ml) on permeability in bEnd.3 cells under hypoglycemic conditions by measuring the ability of Na-F to cross the cell monolayer 24 h after 0.5 mM glucose treatment. As shown in Fig. 4a, a 24 h exposure to 0.5 mM glucose in presence of VEGF decreased the Na-F permeability by 30.8 % compared with 0.5 mM glucose, suggesting the presence of VEGF significantly decreased the enhanced endothelial permeability caused by hypoglycemia.Fig. 4

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