3-Iodothyronamine Activates a Set of Membrane Proteins in Murine Hypothalamic Cell Lines
dc.contributor.author | Bräunig, Julia | |
dc.contributor.author | Mergler, Stefan | |
dc.contributor.author | Jyrch, Sabine | |
dc.contributor.author | Hoefig, Carolin S. | |
dc.contributor.author | Rosowski, Mark | |
dc.contributor.author | Mittag, Jens | |
dc.contributor.author | Biebermann, Heike | |
dc.contributor.author | Khajavi, Noushafarin | |
dc.date.accessioned | 2019-08-12T14:29:34Z | |
dc.date.available | 2019-08-12T14:29:34Z | |
dc.date.issued | 2018-09-11 | |
dc.date.updated | 2019-08-11T01:17:43Z | |
dc.description.abstract | 3-Iodothyronamine (3-T1AM) is an endogenous thyroid hormone metabolite. The profound pharmacological effects of 3-T1AM on energy metabolism and thermal homeostasis have raised interest to elucidate its signaling properties in tissues that pertain to metabolic regulation and thermogenesis. Previous studies identified G protein-coupled receptors (GPCRs) and transient receptor potential channels (TRPs) as targets of 3-T1AM in different cell types. These two superfamilies of membrane proteins are largely expressed in tissue which influences energy balance and metabolism. As the first indication that 3-T1AM virtually modulates the function of the neurons in hypothalamus, we observed that intraperitoneal administration of 50 mg/kg bodyweight of 3-T1AM significantly increased the c-FOS activation in the paraventricular nucleus (PVN) of C57BL/6 mice. To elucidate the underlying mechanism behind this 3-T1AM-induced signalosome, we used three different murine hypothalamic cell lines, which are all known to express PVN markers, GT1-7, mHypoE-N39 (N39) and mHypoE-N41 (N41). Various aminergic GPCRs, which are the known targets of 3-T1AM, as well as numerous members of TRP channel superfamily, are expressed in these cell lines. Effects of 3-T1AM on activation of GPCRs were tested for the two major signaling pathways, the action of Gαs/adenylyl cyclase and Gi/o. Here, we demonstrated that this thyroid hormone metabolite has no significant effect on Gi/o signaling and only a minor effect on the Gαs/adenylyl cyclase pathway, despite the expression of known GPCR targets of 3-T1AM. Next, to test for other potential mechanisms involved in 3-T1AM-induced c-FOS activation in PVN, we evaluated the effect of 3-T1AM on the intracellular Ca2+ concentration and whole-cell currents. The fluorescence-optic measurements showed a significant increase of intracellular Ca2+ concentration in the three cell lines in the presence of 10 μM 3-T1AM. Furthermore, this thyroid hormone metabolite led to an increase of whole-cell currents in N41 cells. Interestingly, the TRPM8 selective inhibitor (10 μM AMTB) reduced the 3-T1AM stimulatory effects on cytosolic Ca2+ and whole-cell currents. Our results suggest that the profound pharmacological effects of 3-T1AM on selected brain nuclei of murine hypothalamus, which are known to be involved in energy metabolism and thermoregulation, might be partially attributable to TRP channel activation in hypothalamic cells. | en |
dc.identifier.eissn | 1664-2392 | |
dc.identifier.uri | https://depositonce.tu-berlin.de/handle/11303/9760 | |
dc.identifier.uri | http://dx.doi.org/10.14279/depositonce-8793 | |
dc.language.iso | en | en |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en |
dc.subject.ddc | 610 Medizin und Gesundheit | de |
dc.subject.other | 3-T1AM | en |
dc.subject.other | signaling | en |
dc.subject.other | hypothalamus | en |
dc.subject.other | GPCR | en |
dc.subject.other | TRP Channel | en |
dc.title | 3-Iodothyronamine Activates a Set of Membrane Proteins in Murine Hypothalamic Cell Lines | en |
dc.type | Article | en |
dc.type.version | publishedVersion | en |
dcterms.bibliographicCitation.articlenumber | 523 | en |
dcterms.bibliographicCitation.doi | 10.3389/fendo.2018.00523 | en |
dcterms.bibliographicCitation.journaltitle | Frontiers in Endocrinology | en |
dcterms.bibliographicCitation.originalpublishername | Frontiers Media S.A. | en |
dcterms.bibliographicCitation.originalpublisherplace | Lausanne | en |
dcterms.bibliographicCitation.volume | 9 | en |
tub.accessrights.dnb | free | en |
tub.affiliation | Fak. 3 Prozesswissenschaften::Inst. Biotechnologie::FG Medizinische Biotechnologie | de |
tub.affiliation.faculty | Fak. 3 Prozesswissenschaften | de |
tub.affiliation.group | FG Medizinische Biotechnologie | de |
tub.affiliation.institute | Inst. Biotechnologie | de |
tub.publisher.universityorinstitution | Technische Universität Berlin | en |
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