Activities per year
(CAPs), inhibition of which in cystic fibrosis has been shown to increase airways surface liquid and normalise mucociliary clearance (MCC)1. These proteases have potential to be therapeutic targets in other chronic airways diseases. This study investigated the ability of natural peptide TL inhibitors, derived from amphibian skin secretions, to inactivate ENaC via CAP inhibition.
Initial screening of the frog peptides was conducted using FRT cells stably transfected with ENaC and changes in fluorescence intensity (FLIPR) utilised to measure ENaC activity. Second round testing was performed using primary differentiated human airway epithelial cells (hAECs) by measurement of IEQ (equivalent short-circuit current) (TECC-24; EP Devices).
FLIPR revealed that all of the frog peptides significantly inhibited
ENaC, particularly QUB-1916 which elicited almost immediate,
complete channel inhibition. Different trends were observed when
the peptides were tested on hAECs using short-circuit current,
with other peptides demonstrating superior ENaC inhibition compared to QUB-1916. Initial profiling indicates a differential protease expression pattern between cell types which may underlie this discrepancy.
These findings highlight the importance of direct testing of channel activity using hAECs. Potential lead compounds are currently being evaluated for efficacy in airway hydration and MCC
- interreg va
John Lockhart (Invited speaker)
Activity: Participating in or organising an event › Participation in workshop, seminar, course
John Lockhart, Gary Litherland, Anne Crilly, Carl Goodyear, Andrew MacKenzie, Iain McLellan, Andisheh Bakhshi, Lynette Dunning, Robin Freeburn, William MacKay, Craig Williams, Kirsty McCallum, Mariarca Bailo, Kimberly Black, Bryn Short, Mark Thomas & Fawziye Tarhini
1 Media contribution
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