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Targeting Aquaporin...
Targeting Aquaporin-4 Subcellular Localization to Treat Central Nervous System Edema
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- Kitchen, Philip (author)
- Aston University
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- Salman, Mootaz M. (author)
- Boston Children's Hospital,Harvard Medical School
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- Halsey, Andrea M. (author)
- University of Birmingham
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- Clarke-Bland, Charlotte (author)
- Aston University
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- MacDonald, Justin A. (author)
- University of Calgary
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- Ishida, Hiroaki (author)
- University of Calgary
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- Vogel, Hans J. (author)
- University of Calgary
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- Almutiri, Sharif (author)
- University of Birmingham
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- Logan, Ann (author)
- University of Birmingham
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- Kreida, Stefan (author)
- Lund University,Lunds universitet,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
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- Al-Jubair, Tamim (author)
- Lund University,Lunds universitet,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
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- Winkel Missel, Julie (author)
- University of Copenhagen
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- Gourdon, Pontus (author)
- Lund University,Lunds universitet,Membranproteinstrukturbiologi,Forskargrupper vid Lunds universitet,Membrane Protein Structural Biology,Lund University Research Groups,University of Copenhagen
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- Törnroth-Horsefield, Susanna (author)
- Lund University,Lunds universitet,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
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- Conner, Matthew T. (author)
- University of Wolverhampton
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- Ahmed, Zubair (author)
- University of Birmingham
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- Conner, Alex C. (author)
- University of Birmingham
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- Bill, Roslyn M. (author)
- Aston University
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(creator_code:org_t)
- Elsevier BV, 2020
- 2020
- English.
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In: Cell. - : Elsevier BV. - 0092-8674. ; 181:4, s. 19-799
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http://dx.doi.org/10... (free)
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http://www.cell.com/...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Swelling of the brain or spinal cord (CNS edema) affects millions of people every year. All potential pharmacological interventions have failed in clinical trials, meaning that symptom management is the only treatment option. The water channel protein aquaporin-4 (AQP4) is expressed in astrocytes and mediates water flux across the blood-brain and blood-spinal cord barriers. Here we show that AQP4 cell-surface abundance increases in response to hypoxia-induced cell swelling in a calmodulin-dependent manner. Calmodulin directly binds the AQP4 carboxyl terminus, causing a specific conformational change and driving AQP4 cell-surface localization. Inhibition of calmodulin in a rat spinal cord injury model with the licensed drug trifluoperazine inhibited AQP4 localization to the blood-spinal cord barrier, ablated CNS edema, and led to accelerated functional recovery compared with untreated animals. We propose that targeting the mechanism of calmodulin-mediated cell-surface localization of AQP4 is a viable strategy for development of CNS edema therapies.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- AQP4
- Aquaporin
- astrocyte
- calmodulin
- edema
- oedema
- protein kinase A
- spinal cord injury
- traumatic brain injury
- trifluoperazine
- TRPV4
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Kitchen, Philip
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Salman, Mootaz M ...
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Halsey, Andrea M ...
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Clarke-Bland, Ch ...
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MacDonald, Justi ...
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Ishida, Hiroaki
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show more...
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Vogel, Hans J.
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Almutiri, Sharif
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Logan, Ann
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Kreida, Stefan
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Al-Jubair, Tamim
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Winkel Missel, J ...
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Gourdon, Pontus
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Törnroth-Horsefi ...
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Conner, Matthew ...
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Ahmed, Zubair
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Conner, Alex C.
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Bill, Roslyn M.
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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Cell
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Lund University