Protein Blotting Handbook: 6th Edition
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- Technical Information
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A role for a CXCR2/phosphatidylinositol 3-kinase gamma signaling axis in acute and chronic vascular permeability.
- Most proangiogenic polypeptide growth factors and chemokines enhance vascular permeability, including vascular endothelial growth factor (VEGF), the main target for anti-angiogenic-based therapies, and interleukin-8 (IL-8), a potent proinflammatory mediator. Here, we show that in endothelial cells IL-8 initiates a signaling route that converges with that deployed by VEGF at the level of the small GTPase Rac1 and that both act through the p21-activated kinase to promote the phosphorylation and internalization of VE-cadherin. However, whereas VEGF activates Rac1 through Src-related kinases, IL-8 specifically signals to Rac1 through its cognate G protein-linked receptor, CXCR2, and the stimulation of the phosphatidylinositol 3-kinase gamma (PI3Kgamma) catalytic isoform, thereby providing a specific molecular targeted intervention in vascular permeability. These results prompted us to investigate the potential role of IL-8 signaling in a mouse model for retinal vascular hyperpermeability. Importantly, we observed that IL-8 is upregulated upon laser-induced retinal damage, which recapitulates enhanced vascularization, leakage, and inflammatory responses. Moreover, blockade of CXCR2 and PI3Kgamma was able to limit neovascularization and choroidal edema, as well as macrophage infiltration, therefore contributing to reduce retinal damage. These findings indicate that the CXCR2 and PI3Kgamma signaling pathway may represent a suitable target for the development of novel therapeutic strategies for human diseases characterized by vascular leakage.
- Document Type:
- Reference
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- Multiple
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- Multiple
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Immobilon -P Blotting Sandwiches
- Document Type:
- User Guide
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- Multiple
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- Multiple
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Immobilon®-P Transfer Membrane User Guide
- Document Type:
- User Guide
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- Multiple
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- Multiple
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Western Blotting Tools
- Document Type:
- Brochure
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- Multiple
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- Multiple
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Immobilon Transfer Membranes: For superior protein and nucleic acid blots
- Document Type:
- Data Sheet
- Product Catalog Number:
- Multiple
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- Multiple
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Analysis of neuronal cell death in mammals.
- Apoptosis, often defined as programmed cell death, plays a very important role in many physiologic and pathologic conditions. Therefore, detecting apoptotic cells or monitoring the cells progressing to apoptosis is an essential step in basic and/or applied research. Apoptosis is characterized by many biologic and morphologic changes of cells, for example, cytochrome c release from mitochondria, activation of caspases, DNA fragmentation, membrane blebbing, and formation of apoptotic bodies. On the basis of these changes, various assays have been designed to detect or quantify apoptotic cells. The goal of this chapter is to provide readers with a scientific guide to proven methods that highlight the current strategies for detecting apoptosis in the nervous system.
- Document Type:
- Reference
- Product Catalog Number:
- MAB1598
- Product Catalog Name:
- Anti-Post Synaptic Density Protein 95 Antibody, clone 7E3-1B8