Endothelin-1 discussed at ISNVD 2015
Posted: Sat Mar 28, 2015 3:43 pm
https://isnvd.org/d/sites/default/files ... %20all.pdf
Is there a role for mast cells dependent synthesis of Endothelin-1 in
neurodegenerative diseases?
Pedro D’Orléans-Juste-1
, Louisane Desbiens, Denis Gris-2
Departments of Pharmacoly-1 and of Pediatrics-2
, Faculty of Medicine,
Université de Sherbrooke, Sherbrooke, PQ, Canada
Abstract:
Background: In the central nervous system mast cells are found in proximity of neurons and blood vessels. During inflammation, activated mastocytes releases several proteases among which chymase is known to generate the potent vasoactive peptide, Endothelin-1 (ET-1). It is of interest that both mast cell density and ET-1 levels are significantly increased in neurological disorders such as Multiple Sclerosis. Principal Aim: To identify the contribution of chymase and ET-1 in a murine model of experimental allergic encephalomyelitis (EAE).
Methods: The ET-1 producing capacity of a mouse chymase isoform Mast Cell Protease 4 (mMCP-4) will be compared to that of its human isoform using a combined recombinant/triple tof mass spectrometry approach. In addition, the contribution of systemic mMCP-4 in radiotelemetry instrumented-conscious mice will be assessed. Finally, clinical scores (from 0, normal mouse to 5, moribund state) will be assessed in WT or mMCP-4 KO mice with induced EAE.
Results and Conclusions: The present study demonstrates that both mouse and human chymases are involved in the synthesis of ET-1. Furthermore, preliminary results show reduced morbidity of EAE-induced mice genetically repressed for mMCP-4. We conclude that among several proteases secreted by mast cells in the vicinity of spinal lesions, chymase may play a significant role in the morbid events occurring in the mouse model of Multiple Sclerosis.