Propofol attenuated TNF-α-modulated occludin expression by inhibiting Hif-1α/ VEGF/ VEGFR-2/ ERK signaling pathway in hCMEC/D3 cells.

Abstract

BACKGROUND:

The levels of tight junction proteins (TJs), especially occludin, correlate with blood-brain barrier (BBB) disruption caused by inflammation in central nervous system (CNS). It has been reported that propofol, the most commonly used anesthetic, could inhibit inflammation response in CNS. In this study, we investigated the effects of tumor necrosis factor-α (TNF-α) and propofol on occludin expression in human cerebral microvascular endothelial cell line, D3 clone (hCMEC/D3 cells), and explored the underlying mechanisms.

METHODS:

The hCMEC/D3 cells were treated with propofol, followed by TNF-α. The expression and phosphorylation of Hif-1α, VEGF, VEGFR-2, ERK, p38MAPK and occludin were measured by Western blot analysis. The cell viability of hCMEC/D3 cells was measured by cell counting kit-8.

RESULTS:

TNF-α (10 ng/ml, 4 h) significantly decreased the expression of occludin, which was attenuated by propofol (25 μM). TNF-α induced Hif-1α/VEGF/VEGFR-2/ERK signaling pathway, while propofol could inhibit it. TNF-α induced the phosphorylation of p38MAPK, while propofol had no effect on it. In addition, the inhibitors of Hif-1α, VEGFR-2, and ERK could reduce the effect of TNF-α on occludin expression.

CONCLUSION:

TNF-α could decrease the expression of occludin via activating Hif-1α/ VEGF/ VEGFR-2/ ERK signaling pathway, which was attenuated by propofol.

• Authors: Yue Zhang, Xiaowei Ding, Changhong Miao, Jiawei Chen
• Journal: BMC anesthesiology (BMC Anesthesiol) Vol. 19 Issue 1 Pg. 127 (07 09 2019) ISSN: 1471-2253 [Electronic] England
• PMID: 31288745 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anesthetics, Intravenous
• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• Occludin
• Tumor Necrosis Factor-alpha
• Vascular Endothelial Growth Factor A
• Vascular Endothelial Growth Factor Receptor-2
• Propofol

Topics

• Anesthetics, Intravenous (pharmacology)
• Cell Line
• Cell Survival (drug effects)
• Endothelial Cells (metabolism)
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (drug effects)
• MAP Kinase Signaling System (drug effects)
• Occludin (metabolism)
• Phosphorylation (drug effects)
• Propofol (pharmacology)
• Signal Transduction (drug effects)
• Tumor Necrosis Factor-alpha (metabolism)
• Vascular Endothelial Growth Factor A (drug effects)
• Vascular Endothelial Growth Factor Receptor-2 (drug effects)