Regulatory control of the Na-Cl co-transporter NCC and its therapeutic potential for hypertension
dc.contributor.author | Meor Azlan, NF | |
dc.contributor.author | Koeners, MP | |
dc.contributor.author | Zhang, J | |
dc.date.accessioned | 2020-09-28T10:09:57Z | |
dc.date.issued | 2020-09-22 | |
dc.description.abstract | Hypertension is the largest risk factor for cardiovascular disease, the leading cause of mortality worldwide. As blood pressure regulation is influenced by multiple physiological systems, hypertension cannot be attributed to a single identifiable etiology. Three decades of research into Mendelian forms of hypertension implicated alterations in the renal tubular sodium handling, particularly the distal convoluted tubule (DCT)-native, thiazide-sensitive Na–Cl cotransporter (NCC). Altered functions of the NCC have shown to have profound effects on blood pressure regulation as illustrated by the over activation and inactivation of the NCC in Gordon’s and Gitelman syndromes respectively. Substantial progress has uncovered multiple factors that affect the expression and activity of the NCC. In particular, NCC activity is controlled by phosphorylation/dephosphorylation, and NCC expression is facilitated by glycosylation and negatively regulated by ubiquitination. Studies have even found parvalbumin to be an unexpected regulator of the NCC. In recent years, there have been considerable advances in our understanding of NCC control mechanisms, particularly via the pathway containing the with-no-lysine [K] (WNK) and its downstream target kinases, SPS/Ste20-related proline-alanine-rich kinase (SPAK) and oxidative stress responsive 1 (OSR1), which has led to the discovery of novel inhibitory molecules. This review summarizes the currently reported regulatory mechanisms of the NCC and discusses their potential as therapeutic targets for treating hypertension. | en_GB |
dc.description.sponsorship | National Institutes of Health | en_GB |
dc.description.sponsorship | University of Exeter Medical School | en_GB |
dc.identifier.citation | Published online 22 September 2020 | en_GB |
dc.identifier.doi | 10.1016/j.apsb.2020.09.009 | |
dc.identifier.grantnumber | 5R01NS109358-02 / Subaward No. GR108129 (CON-80002077) | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/123017 | |
dc.language.iso | en | en_GB |
dc.publisher | Elsevier | en_GB |
dc.rights | © 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. All rights reserved. This is an open access article Under a Creative Commons license : https://creativecommons.org/licenses/by-nc-nd/4.0/ | en_GB |
dc.subject | NaCl-cotransporter NCC | en_GB |
dc.subject | Cardiovascular disease | en_GB |
dc.subject | CUL3/KLHL3-WNK-SPAK/OSR1 | en_GB |
dc.subject | Blood pressure regulation | en_GB |
dc.subject | Kinase inhibitors | en_GB |
dc.subject | Membrane trafficking | en_GB |
dc.subject | Therapeutic targets | en_GB |
dc.subject | Hypertension | en_GB |
dc.title | Regulatory control of the Na-Cl co-transporter NCC and its therapeutic potential for hypertension | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2020-09-28T10:09:57Z | |
dc.identifier.issn | 2211-3835 | |
dc.description | This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record. | en_GB |
dc.identifier.journal | Acta Pharmaceutica Sinica B | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | en_GB |
dcterms.dateAccepted | 2020-09-09 | |
exeter.funder | ::National Institutes of Health | en_GB |
rioxxterms.version | AM | en_GB |
rioxxterms.licenseref.startdate | 2020-09-09 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2020-09-28T10:05:59Z | |
refterms.versionFCD | AM | |
refterms.dateFOA | 2020-09-28T10:10:03Z | |
refterms.panel | A | en_GB |
Files in this item
This item appears in the following Collection(s)
Except where otherwise noted, this item's licence is described as © 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of
Medical Sciences. Production and hosting by Elsevier B.V. All rights reserved. This is an open access article Under a Creative Commons license : https://creativecommons.org/licenses/by-nc-nd/4.0/