Type 3 muscarinic acetylcholine receptor stimulation is a determinant of endothelial barrier function and adherens junctions integrity: role of protein-tyrosine phosphatase 1B
| Autor: | Xin-Ling Du, Chao Liu, Jing Wu, Wen-Zeng Zhao, Bing Wen, Zhou-Yang Jiao |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
medicine.medical_specialty
Cell Membrane Permeability Protein Kinase C-alpha Beta-catenin M3R Biochemistry Dephosphorylation Adherens junction chemistry.chemical_compound VE-cadherin Antigens CD Internal medicine Muscarinic acetylcholine receptor Cyclic AMP Human Umbilical Vein Endothelial Cells medicine Humans Cyclic adenosine monophosphate Phosphorylation Phosphotyrosine Protein kinase A Molecular Biology beta Catenin Research Articles Protein Tyrosine Phosphatase Non-Receptor Type 1 Receptor Muscarinic M3 biology PTP1B Tyrosine phosphorylation Adherens Junctions General Medicine β-catenin Cadherins Receptors Muscarinic Cell biology Endocrinology chemistry biology.protein Endothelium Vascular |
| Zdroj: | BMB Reports |
| ISSN: | 1976-6696 |
| DOI: | 10.5483/bmbrep.2014.47.10.216 |
| Popis: | The main purpose of this study was to investigate whether type 3 muscarinic acetylcholine receptor (M3R) dysfunction induced vascular hyperpermeability. Transwell system analysis showed that M3R inhibition by selective antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) and small interfering RNA both increased endothelial permeability. Using coimmunoprecipitation and Western blot assay, we found that M3R inhibition increased VE-cadherin and β-catenin tyrosine phosphorylation without affecting their expression. Using PTP1B siRNA, we found that PTP1B was required for maintaining VE-cadherin and β-catenin protein dephosphorylation. In addition, 4-DAMP suppressed PTP1B activity by reducing cyclic adenosine monophosphate (cAMP), but not protein kinase Cα (PKCα). These data indicate that M3R preserves the endothelial barrier function through a mechanism potentially maintaining PTP1B activity, keeping the adherens junction proteins (AJPs) dephosphorylation. [BMB Reports 2014; 47(10): 552-557] |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|