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Control of Bioamine Metabolism by 5‐HT 2B and α 1D Autoreceptors through Reactive Oxygen Species and Tumor Necrosis Factor‐α Signaling in Neuronal Cells
Author(s) -
SCHNEIDER BENOIT,
PIETRI MATHÉA,
MOUILLETRICHARD SOPHIE,
ERMONVAL MYRIAM,
MUTEL VINCENT,
LAUNAY JEANMARIE,
KELLERMANN ODILE
Publication year - 2006
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1378.061
Subject(s) - microbiology and biotechnology , receptor , nadph oxidase , serotonergic , autoreceptor , signal transduction , biology , reactive oxygen species , serotonin , chemistry , biochemistry
Homeostasis of the central nervous system relies on the proper integration of cell‐signaling pathways recruited by a variety of neuronal and non‐neuronal factors, with the aim of tightly controlling neurotransmitter metabolism, storage, and transport. We took advantage of the 1C11 neuroectodermal cell line, endowed with the capacity to selectively differentiate into serotonergic (1C11 5–HT ) or noradrenergic (1C11 NE ) neurons, to identify functional targets of serotonin (5‐hydroxytryptamine [5–HT]) and norepinephrine (NE) autoreceptors possibly involved in the control of neuronal functions. We demonstrate that 5‐HT 2B and adreno α 1D receptors are coupled to reactive oxygen species (ROS) production through NADPH oxidase activation in 1C11 5–HT and 1C11 NE neuronal cells, respectively. In the signaling cascade linking 5–HT 2B receptors to NADPH oxidase, phospholipase A2‐mediated arachidonic acid production is required for ROS synthesis. ROS, in turn, act as second message signals and control the activation of TACE (TNF‐α converting enzyme), a member of a disintegrin and metalloproteinase family. 5–HT 2B and α 1D receptor stimulation triggers TACE‐dependent TNF‐α shedding in the surrounding milieu of 1C11 5–HT and 1C11 NE cells. In these cells, shed TNF‐α triggers degradation of 5‐HT and NE into 5‐HIAA and MHPG, respectively. Finally, we observe that 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 neuronal phenotype. Altogether, our data indicate that couplings of 5‐HT 2B and α 1D autoreceptors to ROS and TNF‐α signaling control neurotransmitter metabolism in 1C11‐derived neuronal cells. Eventually, we might explain the origin of oxidative stress and high level of TNF‐α in neurodegenerative diseases as a consequence of deviation of normal signaling pathways coupled to neurotransmitters.