Logo image
Back
Pertussis toxin induces angiogenesis in brain microvascular endothelial cells
Journal article   Peer reviewed

Pertussis toxin induces angiogenesis in brain microvascular endothelial cells

Changming Lu, Steven Pelech, Hong Zhang, Jeffrey Bond, Karen Spach, Rajkumar Noubade, Elizabeth P Blankenhorn and Cory Teuscher
Journal of neuroscience research, v 86(12), pp 2624-2640
Sep 2008
DOI: https://doi.org/10.1002/jnr.21716
PMID: 18500752
Featured in Collection :   UN Sustainable Development Goals @ Drexel

Abstract

Endothelium, Vascular - cytology Neovascularization, Physiologic - drug effects Microcirculation - genetics Cerebrovascular Circulation - physiology Oligonucleotide Array Sequence Analysis Endothelium, Vascular - drug effects Cerebrovascular Circulation - genetics Brain - physiology Microcirculation - drug effects Endothelium, Vascular - physiology Microcirculation - physiology Brain - blood supply Inflammation Mediators - pharmacology Endothelial Cells - physiology Pertussis Toxin - pharmacology Cerebrovascular Circulation - drug effects Neovascularization, Physiologic - genetics Mice, Inbred C57BL Cells, Cultured Mice, Inbred C3H Brain - drug effects Gene Expression Regulation - drug effects Neovascularization, Physiologic - physiology Animals Mice Endothelial Cells - drug effects
Pertussis toxin (PTX) is an ancillary adjuvant used to elicit experimental allergic encephalomyelitis (EAE), the principal autoimmune model of multiple sclerosis. One mechanism whereby PTX potentiates EAE is to increase blood-brain barrier (BBB) permeability. To elucidate further the mechanism of action of PTX on the BBB, we investigated the genomic and proteomic responses of isolated mouse brain endothelial cells (MBEC) following intoxication. Among approximately 14,000 mouse genes tracked by cDNA microarray, 34 showed altered expression in response to PTX. More than one-third of these genes have roles in angiogenesis. Accordingly, we show that intoxication of MBEC induces tube formation in vitro and angiogenesis in vivo. The global effect of PTX on signaling protein levels and phosphorylation in MBEC was investigated by using Kinex antibody microarrays. In total, 113 of 372 pan-specific and 58 of 258 phospho-site-specific antibodies revealed changes >or=25% following intoxication. Increased STAT1 Tyr-701 and Ser-727 phosphorylation; reduced phosphorylation of the activating phospho-sites in Erk1, Erk2, and MAPKAPK2; and decreased phosphorylation of arrestin beta1 Ser-412 and Hsp27 Ser-82 were confirmed by Kinetworks multi-immunoblotting. The importance of signal transduction pathways on PTX-induced MBEC tube formation was evaluated pharmacologically. Inhibition of phospholipase C, MEK1, and p38 MAP kinase had little effect, whereas inhibition of cAMP-dependent protein kinase, protein kinase C, and phosphatidylinositol 3-kinase partially blocked tube formation. Taken together, these findings are consistent with the concept that PTX may lead to increased BBB permeability by altering endothelial plasticity and angiogenesis.

Metrics

8 Record Views
37 citations in Web of Science
39 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Neurosciences
Logo image