Identification of a novel Brain Derived Neurotrophic Factor (BDNF)-inhibitory factor: Regulation of BDNF by Teneurin C-terminal Associated Peptide (TCAP)-1 in immortalized embryonic mouse hypothalamic cells
Autor: | Tiffany Ng, John D. Watson, Dhan Chand, Paul C. Boutros, Arij Al Chawaf, David A. Lovejoy, Lifang Song, Denise D. Belsham |
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Rok vydání: | 2012 |
Předmět: |
Physiology
Clinical Biochemistry Cell Hypothalamus Nerve Tissue Proteins Polymerase Chain Reaction Biochemistry Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Endocrinology Western blot Neurotrophic factors medicine Animals RNA Messenger 030304 developmental biology Brain-derived neurotrophic factor Teneurin 0303 health sciences biology medicine.diagnostic_test Brain-Derived Neurotrophic Factor Embryo Mammalian Molecular biology In vitro Transmembrane protein Cytosol medicine.anatomical_structure biology.protein 030217 neurology & neurosurgery |
Zdroj: | Regulatory Peptides. 174:79-89 |
ISSN: | 0167-0115 |
Popis: | The teneurins are a family of four large transmembrane proteins that are highly expressed in the central nervous system (CNS) where they have been implicated in development and CNS function. At the tip of the carboxyl terminus of each teneurin lies a 43-amino acid sequence, that when processed, could liberate an amidated 41-residue peptide. We have called this region the teneurin C-terminal associated peptide (TCAP). Picomolar concentrations of the synthetic version of TCAP-1 inhibit stress-induced cocaine reinstatement in rats. Because cocaine-seeking is associated with increased brain derived neurotrophic factor (BDNF) in the brain, we examined whether synthetic mouse TCAP-1 has the potential to regulate BDNF expression in immortalized mouse neurons. Immortalized mouse neurons (N38; mHypoE38) show strong FITC-labeled [K 8 ]-TCAP-1 uptake and BDNF labeling in the cytosol. Moreover, FITC-labeled [K 8 ]-TCAP-1 bound competitively to membrane fractions. In culture, the labeled TCAP-1 peptide could be detected on cell membranes within 15 min and subsequently became internalized in the cytosol and trafficked toward the nucleus. Administration of 10 − 8 M unlabeled TCAP-1 to cultures of the N38 cells resulted in a significant decrease of total cell BDNF immunoreactivity over 4 h as determined by western blot and ELISA analyses. Real-time PCR, utilizing primers to the various BDNF transcripts showed a significant decline of promoter IIB- and VI-driven transcripts. Taken together, these studies indicated that in vitro, TCAP-1 induces a significant decline in BDNF transcription and protein labeling in embyronic mouse immortalized hypothalamic neurons. Thus, TCAP-1 may act as a novel BDNF inhibitory factor. |
Databáze: | OpenAIRE |
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