Integration of TRPC6 and NADPH oxidase activation in lysophosphatidylcholine-induced TRPC5 externalization

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 TRP...

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Autores principales: Chaudhuri, Pinaki, Rosenbaum, Michael A., Birnbaumer, Lutz, Graham, Linda M.
Formato: Artículo
Lenguaje:Inglés
Publicado: American Physiological Society 2019
Materias:
CLACIO
ENDOTELIO
PROTEINAS
GENES
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/8721
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139123456789-8721
record_format dspace
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic CLACIO
ENDOTELIO
PROTEINAS
GENES
spellingShingle CLACIO
ENDOTELIO
PROTEINAS
GENES
Chaudhuri, Pinaki
Rosenbaum, Michael A.
Birnbaumer, Lutz
Graham, Linda M.
Integration of TRPC6 and NADPH oxidase activation in lysophosphatidylcholine-induced TRPC5 externalization
topic_facet CLACIO
ENDOTELIO
PROTEINAS
GENES
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.
format Artículo
author Chaudhuri, Pinaki
Rosenbaum, Michael A.
Birnbaumer, Lutz
Graham, Linda M.
author_facet Chaudhuri, Pinaki
Rosenbaum, Michael A.
Birnbaumer, Lutz
Graham, Linda M.
author_sort Chaudhuri, Pinaki
title Integration of TRPC6 and NADPH oxidase activation in lysophosphatidylcholine-induced TRPC5 externalization
title_short Integration of TRPC6 and NADPH oxidase activation in lysophosphatidylcholine-induced TRPC5 externalization
title_full Integration of TRPC6 and NADPH oxidase activation in lysophosphatidylcholine-induced TRPC5 externalization
title_fullStr Integration of TRPC6 and NADPH oxidase activation in lysophosphatidylcholine-induced TRPC5 externalization
title_full_unstemmed Integration of TRPC6 and NADPH oxidase activation in lysophosphatidylcholine-induced TRPC5 externalization
title_sort integration of trpc6 and nadph oxidase activation in lysophosphatidylcholine-induced trpc5 externalization
publisher American Physiological Society
publishDate 2019
url https://repositorio.uca.edu.ar/handle/123456789/8721
work_keys_str_mv AT chaudhuripinaki integrationoftrpc6andnadphoxidaseactivationinlysophosphatidylcholineinducedtrpc5externalization
AT rosenbaummichaela integrationoftrpc6andnadphoxidaseactivationinlysophosphatidylcholineinducedtrpc5externalization
AT birnbaumerlutz integrationoftrpc6andnadphoxidaseactivationinlysophosphatidylcholineinducedtrpc5externalization
AT grahamlindam integrationoftrpc6andnadphoxidaseactivationinlysophosphatidylcholineinducedtrpc5externalization
bdutipo_str Repositorios
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