دورية أكاديمية
BDNF- and VEGF-Responsive Stimulus to an NGF Mimic Cyclic Peptide with Copper Ionophore Capability and Ctr1/CCS-Driven Signaling.
| العنوان: | BDNF- and VEGF-Responsive Stimulus to an NGF Mimic Cyclic Peptide with Copper Ionophore Capability and Ctr1/CCS-Driven Signaling. |
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| المؤلفون: | Tomasello B; Department of Drug and Health Sciences, University of Catania, V.le Andrea Doria 6, Catania 95125, Italy., Bellia F; Institute of Crystallography, CNR, P. Gaifami 18, Catania 95126, Italy., Naletova I; Institute of Crystallography, CNR, P. Gaifami 18, Catania 95126, Italy., Magrì A; Institute of Crystallography, CNR, P. Gaifami 18, Catania 95126, Italy., Tabbì G; Institute of Crystallography, CNR, P. Gaifami 18, Catania 95126, Italy., Attanasio F; Institute of Crystallography, CNR, P. Gaifami 18, Catania 95126, Italy., Tomasello MF; Institute of Crystallography, CNR, P. Gaifami 18, Catania 95126, Italy., Cairns WRL; Istituto di Scienze Polari (ISP), c/o Campus Scientifico, Università Ca' Foscari Venezia Via Torino, Venezia Mestre 155-30170, Italy., Fortino M; Dipartimento di Scienze della Salute, Università di Catanzaro, Viale Europa, Catanzaro 88100, Italy., Pietropaolo A; Dipartimento di Scienze della Salute, Università di Catanzaro, Viale Europa, Catanzaro 88100, Italy., Greco V; Department of Chemical Sciences, University of Catania, A. Doria 6, Catania 95125, Italy., La Mendola D; Department of Pharmaceutical Sciences, University of Pisa, Bonanno Pisano 12, Pisa 56126, Italy., Sciuto S; Department of Chemical Sciences, University of Catania, A. Doria 6, Catania 95125, Italy., Arena G; Department of Chemical Sciences, University of Catania, A. Doria 6, Catania 95125, Italy., Rizzarelli E; Institute of Crystallography, CNR, P. Gaifami 18, Catania 95126, Italy.; Department of Chemical Sciences, University of Catania, A. Doria 6, Catania 95125, Italy. |
| المصدر: | ACS chemical neuroscience [ACS Chem Neurosci] 2024 May 01; Vol. 15 (9), pp. 1755-1769. Date of Electronic Publication: 2024 Apr 11. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 101525337 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1948-7193 (Electronic) Linking ISSN: 19487193 NLM ISO Abbreviation: ACS Chem Neurosci Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, D.C. : American Chemical Society |
| مواضيع طبية MeSH: | Nerve Growth Factor*/pharmacology , Nerve Growth Factor*/metabolism , Vascular Endothelial Growth Factor A*/metabolism , Copper*/metabolism , Copper*/pharmacology , Brain-Derived Neurotrophic Factor*/metabolism , Peptides, Cyclic*/pharmacology , Peptides, Cyclic*/chemistry, PC12 Cells ; Animals ; Rats ; Signal Transduction/drug effects ; Signal Transduction/physiology ; Ionophores/pharmacology ; Cation Transport Proteins/metabolism ; Receptor, trkA/metabolism |
| مستخلص: | Neurotrophins are a family of growth factors that play a key role in the development and regulation of the functioning of the central nervous system. Their use as drugs is made difficult by their poor stability, cellular permeability, and side effects. Continuing our effort to use peptides that mimic the neurotrophic growth factor (NGF), the family model protein, and specifically the N-terminus of the protein, here we report on the spectroscopic characterization and resistance to hydrolysis of the 14-membered cyclic peptide reproducing the N-terminus sequence (SSSHPIFHRGEFSV (c-NGF(1-14)). Far-UV CD spectra and a computational study show that this peptide has a rigid conformation and left-handed chirality typical of polyproline II that favors its interaction with the D5 domain of the NGF receptor TrkA. c-NGF(1-14) is able to bind Cu 2+ with good affinity; the resulting complexes have been characterized by potentiometric and spectroscopic measurements. Experiments on PC12 cells show that c-NGF(1-14) acts as an ionophore, influencing the degree and the localization of both the membrane transporter (Ctr1) and the copper intracellular transporter (CCS). c-NGF(1-14) induces PC12 differentiation, mimics the protein in TrkA phosphorylation, and activates the kinase cascade, inducing Erk1/2 phosphorylation. c-NGF(1-14) biological activities are enhanced when the peptide interacts with Cu 2+ even with the submicromolar quantities present in the culture media as demonstrated by ICP-OES measurements. Finally, c-NGF(1-14) and Cu 2+ concur to activate the cAMP response element-binding protein CREB that, in turn, induces the brain-derived neurotrophic factor (BDNF) and the vascular endothelial growth factor (VEGF) release. |
| فهرسة مساهمة: | Keywords: NGF mimics; PC12 cells; copper homeostasis; copper signaling; molecular simulations; trophic factors |
| المشرفين على المادة: | 9061-61-4 (Nerve Growth Factor) 0 (Vascular Endothelial Growth Factor A) 789U1901C5 (Copper) 0 (Brain-Derived Neurotrophic Factor) 0 (Peptides, Cyclic) 0 (Ionophores) 0 (Cation Transport Proteins) EC 2.7.10.1 (Receptor, trkA) 0 (Bdnf protein, rat) |
| تواريخ الأحداث: | Date Created: 20240411 Date Completed: 20240501 Latest Revision: 20240613 |
| رمز التحديث: | 20240614 |
| DOI: | 10.1021/acschemneuro.3c00716 |
| PMID: | 38602894 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 1948-7193 |
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| DOI: | 10.1021/acschemneuro.3c00716 |