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Reactive oxygen species‐dependent TNF‐α converting enzyme activation through stimulation of 5‐HT 2B and α 1D autoreceptors in neuronal cells
Author(s) -
Pietri Mathéa,
Schneider Benoît,
MouilletRichard Sophie,
Ermonval Myriam,
Mutel Vincent,
Launay JeanMarie,
Kellermann Odile
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-3631com
Subject(s) - serotonergic , microbiology and biotechnology , nadph oxidase , autoreceptor , signal transduction , receptor , monoamine oxidase a , biology , reactive oxygen species , context (archaeology) , oxidative stress , neuroscience , chemistry , serotonin , endocrinology , biochemistry , paleontology
A major determinant of neuronal homeostasis is the proper integration of cell signaling pathways recruited by a variety of neuronal and non‐neuronal factors. By taking advantage of a neuroectodermal cell line (1C11) endowed with the capacity to differentiate into serotonergic (1C11 5‐HT ) or noradrenergic (1C11 NE ) neurons, we identified serotonin (5‐hydroxytryptamine, 5‐HT)‐ and norepinephrine (NE)‐dependent signaling cascades possibly involved in neuronal functions. First, we establish that 5‐HT 2B receptors and α 1D adrenoceptors are functionally coupled to reactive oxygen species (ROS) synthesis through NADPH oxidase activation in 1C11 5‐HT and 1C11 NE cells. This observation constitutes the prime evidence that bioaminergic autoreceptors take part in the control of the cellular redox equilibrium in a neuronal context. Second, our data identify TACE (TNF‐α Converting Enzyme), a member of a disintegrin and metalloproteinase (ADAM) family, as a downstream target of the 5‐HT 2B and α 1D receptor‐NADPH oxidase signaling pathways. Upon 5‐HT 2B or α 1D receptor stimulation, ROS fully govern TNF‐α shedding in the surrounding milieu of 1C11 5HT or 1C11 NE cells. Third, 5‐HT 2B and α 1D receptor couplings to the NADPH oxidase‐TACE cascade are strictly restricted to 1C11‐derived progenies that have implemented a complete serotonergic or noradrenergic phenotype. Overall, these observations suggest that 5‐HT 2B and α 1D autoreceptors may play a role in the maintenance of neuron‐ and neurotransmitter‐associated functions. Eventually, our study may have implications regarding the origin of oxidative stress as well as up‐regulated expression of proinflammatory cytokines in neurodegenerative disorders, which may relate to the deviation of normal signaling pathways. Pietri, M., Schneider, B., Mouillet‐Richard, S., Ermonval, M., Mutel, V., Launay, J.‐M., Kellermann, O. Reactive oxygen species‐dependent TNF‐α converting enzyme activation through stimulation of 5‐HT 2B and α 1D autoreceptors in neuronal cells. FASEB J. 19, 1078–1087 (2005)