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Regulatory mechanisms of epithelial sodium channel

Wang, Su (2010)
Ph.D. thesis, University of Birmingham.

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Epithelial sodium channels (ENaC) are of immense importance, controlling Na+ transport across epithelia and thus playing a critical role in all aspects of fluid clearance as well as numerous other functions. Although extensive studies have been carried out to invistegate the regulation mechanism of ENaC, many questions still remain unclear. Therefore, we employed various techniques including electrophysiology and molecular biology approaches to investigate the mechanisms underlying the regulation of ENaCs by lipid metabolites, oxygen and mechanical stress. We have identified profound regulation mechanisms of ENaC in distal renal epithelial cells and vascular endothelial cells by lipid metabolites, heme and mechanical forces. Our results revealed a novel O\(_2\) sensitive regulation pathway of ENaC channels, in which hemeoxygenase acts as the O\(_2\) sensor and the substrate and product of which either inhibits or stimulates ENaC activity. This finding may eventually lead to novel clinic strategies in dealing with diseases e.g. renal failure, kidney reperfusion injury, hypertension, pulmonary edema and pre-clampsia. In addition, we, at the first time, have revealed that ENaC is functionally expressed in a variety of endothelial cells and is able to serve as mechano-transducing sensors in the vascular endothelial cells which play important roles in vascular physiology and pathology progresses.

Type of Work:Ph.D. thesis.
Supervisor(s):Gu, Yuchun
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Clinical and Experimental Medicine
Subjects:RC Internal medicine
QP Physiology
Institution:University of Birmingham
ID Code:1096
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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