Nonmuscle myosin light chain kinase activity modulates radiation-induced lung injury.

Persistent Link:
http://hdl.handle.net/10150/614982
Title:
Nonmuscle myosin light chain kinase activity modulates radiation-induced lung injury.
Author:
Wang, Ting; Mathew, Biji; Wu, Xiaomin; Shimizu, Yuka; Rizzo, Alicia N; Dudek, Steven M; Weichselbaum, Ralph R; Jacobson, Jeffrey R; Hecker, Louise; Garcia, Joe G N
Issue Date:
2016-06
Citation:
Nonmuscle myosin light chain kinase activity modulates radiation-induced lung injury. 2016, 6 (2):234-9 Pulm Circ
Journal:
Pulmonary circulation
Rights:
© 2016 by the Pulmonary Vascular Research Institute. All rights reserved.
Collection Information:
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
Abstract:
Radiotherapy as a primary treatment for thoracic malignancies induces deleterious effects, such as acute or subacute radiation-induced lung injury (RILI). Although the molecular etiology of RILI is controversial and likely multifactorial, a potentially important cellular target is the lung endothelial cytoskeleton that regulates paracellular gap formation and the influx of macromolecules and fluid to the alveolar space. Here we investigate the central role of a key endothelial cytoskeletal regulatory protein, the nonmuscle isoform of myosin light chain kinase (nmMLCK), in an established murine RILI model. Our results indicate that thoracic irradiation significantly augmented nmMLCK protein expression and enzymatic activity in murine lungs. Furthermore, genetically engineered mice harboring a deletion of the nmMLCK gene (nmMLCK(-/-) mice) exhibited protection from RILI, as assessed by attenuated vascular leakage and leukocyte infiltration. In addition, irradiated wild-type mice treated with two distinct MLCK enzymatic inhibitors, ML-7 and PIK (peptide inhibitor of kinase), also demonstrated attenuated RILI. Taken together, these data suggests a key role for nmMLCK in vascular barrier regulation in RILI and warrants further examination of RILI strategies that target nmMLCK.
Note:
Electronically published April 19, 2016. 12 month embargo.
ISSN:
2045-8932
PubMed ID:
27252850
DOI:
10.1086/686491
Version:
Final published version

Full metadata record

DC FieldValue Language
dc.contributor.authorWang, Tingen
dc.contributor.authorMathew, Bijien
dc.contributor.authorWu, Xiaominen
dc.contributor.authorShimizu, Yukaen
dc.contributor.authorRizzo, Alicia Nen
dc.contributor.authorDudek, Steven Men
dc.contributor.authorWeichselbaum, Ralph Ren
dc.contributor.authorJacobson, Jeffrey Ren
dc.contributor.authorHecker, Louiseen
dc.contributor.authorGarcia, Joe G Nen
dc.date.accessioned2016-06-29T00:52:10Z-
dc.date.available2016-06-29T00:52:10Z-
dc.date.issued2016-06-
dc.identifier.citationNonmuscle myosin light chain kinase activity modulates radiation-induced lung injury. 2016, 6 (2):234-9 Pulm Circen
dc.identifier.issn2045-8932-
dc.identifier.pmid27252850-
dc.identifier.doi10.1086/686491-
dc.identifier.urihttp://hdl.handle.net/10150/614982-
dc.description.abstractRadiotherapy as a primary treatment for thoracic malignancies induces deleterious effects, such as acute or subacute radiation-induced lung injury (RILI). Although the molecular etiology of RILI is controversial and likely multifactorial, a potentially important cellular target is the lung endothelial cytoskeleton that regulates paracellular gap formation and the influx of macromolecules and fluid to the alveolar space. Here we investigate the central role of a key endothelial cytoskeletal regulatory protein, the nonmuscle isoform of myosin light chain kinase (nmMLCK), in an established murine RILI model. Our results indicate that thoracic irradiation significantly augmented nmMLCK protein expression and enzymatic activity in murine lungs. Furthermore, genetically engineered mice harboring a deletion of the nmMLCK gene (nmMLCK(-/-) mice) exhibited protection from RILI, as assessed by attenuated vascular leakage and leukocyte infiltration. In addition, irradiated wild-type mice treated with two distinct MLCK enzymatic inhibitors, ML-7 and PIK (peptide inhibitor of kinase), also demonstrated attenuated RILI. Taken together, these data suggests a key role for nmMLCK in vascular barrier regulation in RILI and warrants further examination of RILI strategies that target nmMLCK.en
dc.language.isoenen
dc.rights© 2016 by the Pulmonary Vascular Research Institute. All rights reserved.en
dc.titleNonmuscle myosin light chain kinase activity modulates radiation-induced lung injury.en
dc.typeArticleen
dc.identifier.journalPulmonary circulationen
dc.description.noteElectronically published April 19, 2016. 12 month embargo.en
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen

Related articles on PubMed

All Items in UA Campus Repository are protected by copyright, with all rights reserved, unless otherwise indicated.