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dc.contributor.author
Chaudhuri, Pinaki
dc.contributor.author
Rosenbaum, Michael A.
dc.contributor.author
Birnbaumer, Lutz
dc.contributor.author
Graham, Linda M.
dc.date.available
2018-06-15T17:30:41Z
dc.date.issued
2017-11
dc.identifier.citation
Chaudhuri, Pinaki; Rosenbaum, Michael A.; Birnbaumer, Lutz; Graham, Linda M.; Integration of TRPC6 and NADPH oxidase activation in lysophosphatidylcholine-induced TRPC5 externalization; American Physiological Society; American Journal of Physiology-cell Physiology; 313; 5; 11-2017; 541-555
dc.identifier.issn
0363-6143
dc.identifier.uri
http://hdl.handle.net/11336/48812
dc.description.abstract
Lipid oxidation products, including lysophosphatidylcholine (lysoPC), activate canonical transient receptor potential 6 (TRPC6) channels, and the subsequent increase in intracellular Ca2+ leads to TRPC5 activation. The goal of this study is to elucidate the steps in the pathway between TRPC6 activation and TRPC5 externalization. Following TRPC6 activation by lysoPC, extracellular regulated kinase (ERK) is phosphorylated. This leads to phosphorylation of p47phox and subsequent NADPH oxidase activation with increased production of reactive oxygen species. ERK activation requires TRPC6 opening and influx of Ca2+ as evidenced by the failure of lysoPC to induce ERK phosphorylation in TRPC6−/− endothelial cells. ERK siRNA blocks the lysoPC-induced activation of NADPH oxidase, demonstrating that ERK activation is upstream of NADPH oxidase. The reactive oxygen species produced by NADPH oxidase promote myosin light chain kinase (MLCK) activation with phosphorylation of MLC and TRPC5 externalization. Downregulation of ERK, NADPH oxidase, or MLCK with the relevant siRNA prevents TRPC5 externalization. Blocking MLCK activation prevents the prolonged rise in intracellular calcium levels and preserves endothelial migration in the presence of lysoPC.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
American Physiological Society
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Trpc6
dc.subject
Trpc5
dc.subject
Nadph
dc.subject.classification
Otras Ciencias Biológicas
dc.subject.classification
Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
Integration of TRPC6 and NADPH oxidase activation in lysophosphatidylcholine-induced TRPC5 externalization
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-06-13T15:10:49Z
dc.journal.volume
313
dc.journal.number
5
dc.journal.pagination
541-555
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Bethesda
dc.description.fil
Fil: Chaudhuri, Pinaki. Cleveland Clinic; Estados Unidos
dc.description.fil
Fil: Rosenbaum, Michael A.. Cleveland Clinic; Estados Unidos. Louis Stokes Cleveland Veterans Affairs Medical Center; Estados Unidos
dc.description.fil
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina. Research Triangle Park; Estados Unidos. Cleveland Clinic; Estados Unidos
dc.description.fil
Fil: Graham, Linda M.. Cleveland Clinic; Estados Unidos
dc.journal.title
American Journal of Physiology-cell Physiology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.physiology.org/doi/10.1152/ajpcell.00028.2017
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.1152/ajpcell.00028.2017
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