Nerve growth factor mediates a switch in intracellular signaling for PGE2-induced sensitization of sensory neurons from protein kinase A to Epac.

We examined whether nerve growth factor (NGF), an inflammatory mediator that contributes to chronic hypersensitivity, alters the intracellular signaling that mediates the sensitizing actions of PGE2 from activation of protein kinase A (PKA) to exchange proteins directly activated by cAMP (Epacs). Wh...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Michael R Vasko, Ramy Habashy Malty, Chunlu Guo, Djane B Duarte, Yihong Zhang, Grant D Nicol
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5ba58510d4a94797a3a87966b7efaadb
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:5ba58510d4a94797a3a87966b7efaadb
record_format	dspace
spelling	oai:doaj.org-article:5ba58510d4a94797a3a87966b7efaadb2021-11-25T06:04:30ZNerve growth factor mediates a switch in intracellular signaling for PGE2-induced sensitization of sensory neurons from protein kinase A to Epac.1932-620310.1371/journal.pone.0104529https://doaj.org/article/5ba58510d4a94797a3a87966b7efaadb2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25126967/?tool=EBIhttps://doaj.org/toc/1932-6203We examined whether nerve growth factor (NGF), an inflammatory mediator that contributes to chronic hypersensitivity, alters the intracellular signaling that mediates the sensitizing actions of PGE2 from activation of protein kinase A (PKA) to exchange proteins directly activated by cAMP (Epacs). When isolated sensory neurons are grown in the absence of added NGF, but not in cultures grown with 30 ng/ml NGF, inhibiting protein kinase A (PKA) activity blocks the ability of PGE2 to augment capsaicin-evoked release of the neuropeptide CGRP and to increase the number of action potentials (APs) evoked by a ramp of current. Growing sensory neurons in culture in the presence of increasing concentrations of NGF increases the expression of Epac2, but not Epac1. An intradermal injection of complete Freund's adjuvant into the rat hindpaw also increases the expression of Epac2, but not Epac1 in the dorsal root ganglia and spinal cord: an effect blocked by intraplantar administration of NGF antibodies. Treating cultures grown in the presence of 30 ng/ml NGF with Epac1siRNA significantly reduced the expression of Epac1, but not Epac2, and did not block the ability of PGE2 to augment capsaicin-evoked release of CGRP from sensory neurons. Exposing neuronal cultures grown in NGF to Epac2siRNAreduced the expression of Epac2, but not Epac1 and prevented the PGE2-induced augmentation of capsaicin and potassium-evoked CGRP release in sensory neurons and the PGE2-induced increase in the number of APs generated by a ramp of current. In neurons grown with no added NGF, Epac siRNAs did not attenuate PGE2-induced sensitization. These results demonstrate that NGF, through increasing Epac2 expression, alters the signaling cascade that mediates PGE2-induced sensitization of sensory neurons, thus providing a novel mechanism for maintaining PGE2-induced hypersensitivity during inflammation.Michael R VaskoRamy Habashy MaltyChunlu GuoDjane B DuarteYihong ZhangGrant D NicolPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 8, p e104529 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Michael R Vasko Ramy Habashy Malty Chunlu Guo Djane B Duarte Yihong Zhang Grant D Nicol Nerve growth factor mediates a switch in intracellular signaling for PGE2-induced sensitization of sensory neurons from protein kinase A to Epac.
description	We examined whether nerve growth factor (NGF), an inflammatory mediator that contributes to chronic hypersensitivity, alters the intracellular signaling that mediates the sensitizing actions of PGE2 from activation of protein kinase A (PKA) to exchange proteins directly activated by cAMP (Epacs). When isolated sensory neurons are grown in the absence of added NGF, but not in cultures grown with 30 ng/ml NGF, inhibiting protein kinase A (PKA) activity blocks the ability of PGE2 to augment capsaicin-evoked release of the neuropeptide CGRP and to increase the number of action potentials (APs) evoked by a ramp of current. Growing sensory neurons in culture in the presence of increasing concentrations of NGF increases the expression of Epac2, but not Epac1. An intradermal injection of complete Freund's adjuvant into the rat hindpaw also increases the expression of Epac2, but not Epac1 in the dorsal root ganglia and spinal cord: an effect blocked by intraplantar administration of NGF antibodies. Treating cultures grown in the presence of 30 ng/ml NGF with Epac1siRNA significantly reduced the expression of Epac1, but not Epac2, and did not block the ability of PGE2 to augment capsaicin-evoked release of CGRP from sensory neurons. Exposing neuronal cultures grown in NGF to Epac2siRNAreduced the expression of Epac2, but not Epac1 and prevented the PGE2-induced augmentation of capsaicin and potassium-evoked CGRP release in sensory neurons and the PGE2-induced increase in the number of APs generated by a ramp of current. In neurons grown with no added NGF, Epac siRNAs did not attenuate PGE2-induced sensitization. These results demonstrate that NGF, through increasing Epac2 expression, alters the signaling cascade that mediates PGE2-induced sensitization of sensory neurons, thus providing a novel mechanism for maintaining PGE2-induced hypersensitivity during inflammation.
format	article
author	Michael R Vasko Ramy Habashy Malty Chunlu Guo Djane B Duarte Yihong Zhang Grant D Nicol
author_facet	Michael R Vasko Ramy Habashy Malty Chunlu Guo Djane B Duarte Yihong Zhang Grant D Nicol
author_sort	Michael R Vasko
title	Nerve growth factor mediates a switch in intracellular signaling for PGE2-induced sensitization of sensory neurons from protein kinase A to Epac.
title_short	Nerve growth factor mediates a switch in intracellular signaling for PGE2-induced sensitization of sensory neurons from protein kinase A to Epac.
title_full	Nerve growth factor mediates a switch in intracellular signaling for PGE2-induced sensitization of sensory neurons from protein kinase A to Epac.
title_fullStr	Nerve growth factor mediates a switch in intracellular signaling for PGE2-induced sensitization of sensory neurons from protein kinase A to Epac.
title_full_unstemmed	Nerve growth factor mediates a switch in intracellular signaling for PGE2-induced sensitization of sensory neurons from protein kinase A to Epac.
title_sort	nerve growth factor mediates a switch in intracellular signaling for pge2-induced sensitization of sensory neurons from protein kinase a to epac.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/5ba58510d4a94797a3a87966b7efaadb
work_keys_str_mv	AT michaelrvasko nervegrowthfactormediatesaswitchinintracellularsignalingforpge2inducedsensitizationofsensoryneuronsfromproteinkinaseatoepac AT ramyhabashymalty nervegrowthfactormediatesaswitchinintracellularsignalingforpge2inducedsensitizationofsensoryneuronsfromproteinkinaseatoepac AT chunluguo nervegrowthfactormediatesaswitchinintracellularsignalingforpge2inducedsensitizationofsensoryneuronsfromproteinkinaseatoepac AT djanebduarte nervegrowthfactormediatesaswitchinintracellularsignalingforpge2inducedsensitizationofsensoryneuronsfromproteinkinaseatoepac AT yihongzhang nervegrowthfactormediatesaswitchinintracellularsignalingforpge2inducedsensitizationofsensoryneuronsfromproteinkinaseatoepac AT grantdnicol nervegrowthfactormediatesaswitchinintracellularsignalingforpge2inducedsensitizationofsensoryneuronsfromproteinkinaseatoepac
_version_	1718414224238051328

Nerve growth factor mediates a switch in intracellular signaling for PGE2-induced sensitization of sensory neurons from protein kinase A to Epac.

Ejemplares similares