Role of ATP synthase alpha subunit in low-dose endothelial monocyte-activating polypeptide-II-induced opening of the blood-tumor barrier.

Abstract

This study was performed to determine whether the α subunit of ATP synthase (α-ATP synthase) on brain microvascular endothelial cells (BMECs) serves as the functional target for endothelial monocyte-activating polypeptide-II (EMAP-II)-induced increase in blood-tumor barrier (BTB) permeability. Using a rat C6 glioma model, we found that low-dose (80 ng/kg) EMAP-II significantly decreased the mRNA and protein expression levels of tight junction (TJ)-related proteins claudin-5, occludin, and ZO-1 on BMECs. Meantime, radioimmunity and Western blot assay showed a significant decrease in the expression levels of cAMP and catalytic subunit of protein kinase A (PKAcs) of tumor tissues. Also, pretreatment with specific α-ATP synthase antibody significantly blocked the effects of EMAP-II on TJ-related proteins, cAMP, and PKAcs. In addition, double immunofluorescence assay identified that EMAP-II was co-localized with α-ATP synthase on BMECs. This in vivo study demonstrated that α subunit of ATP synthase on BMECs serves as the functional target for EMAP-II selective opening of the BTB, and that cAMP/PKA signaling transduction pathway might be involved in the modulating process.

• Authors: Zhen Li, Yun-hui Liu, Yi-xue Xue, Hui Xie, Li-bo Liu
• Journal: Journal of the neurological sciences (J Neurol Sci) Vol. 300 Issue 1-2 Pg. 52-8 (Jan 15 2011) ISSN: 1878-5883 [Electronic] Netherlands
• PMID: 21035144 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier B.V. All rights reserved.

Chemical References

• Claudin-5
• Cldn5 protein, rat
• Cytokines
• Membrane Proteins
• Neoplasm Proteins
• Occludin
• Ocln protein, rat
• Phosphoproteins
• Protein Subunits
• RNA-Binding Proteins
• Tjp1 protein, rat
• Zonula Occludens-1 Protein
• small inducible cytokine subfamily E, member 1
• Evans Blue
• Cyclic AMP
• Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
• Mitochondrial Proton-Translocating ATPases
• Proton-Translocating ATPases

Topics

• Animals
• Brain (blood supply, metabolism)
• Capillary Permeability (drug effects, physiology)
• Cell Line, Tumor
• Claudin-5
• Cyclic AMP (metabolism)
• Cyclic AMP-Dependent Protein Kinase Catalytic Subunits (metabolism)
• Cytokines (pharmacology)
• Disease Models, Animal
• Endothelial Cells (drug effects, metabolism)
• Evans Blue (metabolism)
• Glioma (blood supply, metabolism)
• Male
• Membrane Proteins (metabolism)
• Mitochondrial Proton-Translocating ATPases (antagonists & inhibitors, physiology)
• Neoplasm Proteins (pharmacology)
• Occludin
• Phosphoproteins (metabolism)
• Protein Subunits (antagonists & inhibitors, physiology)
• Proton-Translocating ATPases (antagonists & inhibitors, drug effects, physiology)
• RNA-Binding Proteins (pharmacology)
• Rats
• Rats, Wistar
• Zonula Occludens-1 Protein