Garza Carbajal, Anibal, Ebersberger, Andrea, Thiel, Alina, Ferrari, Luiz, Acuna, Jeremy, Brosig, Stephanie, Isensee, Joerg, Moeller, Katharina, Siobal, Maike, Rose-John, Stefan ORCID: 0000-0002-7519-3279, Levine, Jon, Schaible, Hans-Georg and Hucho, Tim . Oncostatin M induces hyperalgesic priming and amplifies signaling of cAMP to ERK by RapGEF2 and PKA. J. Neurochem.. HOBOKEN: WILEY. ISSN 1471-4159
Full text not available from this repository.Abstract
Hyperalgesic priming is characterized by enhanced nociceptor sensitization by pronociceptive mediators, prototypically PGE(2). Priming has gained interest as a mechanism underlying the transition to chronic pain. Which stimuli induce priming and what cellular mechanisms are employed remains incompletely understood. In adult male rats, we present the cytokine OncostatinM(OSM), a member of the IL-6 family, as an inducer of priming by a novel mechanism. We used a high content microscopy based approach to quantify the activation of endogenous PKA-II and ERK of thousands sensory neurons in culture. Incubation with OSM increased and prolonged ERK activation by agents that increase cAMP production such as PGE(2), forskolin, and cAMP analogs. These changes were specific to IB4/CaMKII alpha positive neurons, required protein translation, and increased cAMP-to-ERK signaling. In both, control and OSM-treated neurons, cAMP/ERK signaling involved RapGEF2 and PKA but not Epac. Similar enhancement of cAMP-to-ERK signaling could be induced by GDNF, which acts mostly on IB4/CaMKII alpha-positive neurons, but not by NGF, which acts mostly on IB4/CaMKII alpha-negative neurons. In vitro, OSM pretreatment rendered baseline TTX-R currents ERK-dependent and switched forskolin-increased currents from partial to full ERK-dependence in small/medium sized neurons. In summary, priming induced by OSM uses a novel mechanism to enhance and prolong coupling of cAMP/PKA to ERK1/2 signaling without changing the overall pathway structure.
Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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URN: | urn:nbn:de:hbz:38-318817 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
DOI: | 10.1111/jnc.15172 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Journal or Publication Title: | J. Neurochem. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Publisher: | WILEY | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Place of Publication: | HOBOKEN | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ISSN: | 1471-4159 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Language: | English | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Faculty: | Unspecified | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Divisions: | Unspecified | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subjects: | no entry | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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URI: | http://kups.ub.uni-koeln.de/id/eprint/31881 |
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