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Thankan Jayasekharan, Shyam L Gupta, Vikas Dhiman
The intrinsic binding ability of seven natural peptides (oxytocin, arg8 -vasopressin, bradykinin, angiotensin-I, substance-P, somatostatin, and neurotensin) with copper in two different oxidation states (CuI/II ) derived from different Cu+/2+ precursor sources have been investigated for their charge dependent binding characteristics. The peptide-CuI/II complexes, [M - (n-1)H + nCuI ] and [M - (2n-1)H + nCuII ] are prepared/generated by the reaction of peptides with CuI solution/Cu-target and CuSO4 solution, and are analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS)...
January 15, 2018: Journal of Mass Spectrometry: JMS
Juan Pedro-Botet, David Benaiges
No abstract text is available yet for this article.
January 10, 2018: Obesity
María E Aranda-Barradas, Maripaz Márquez, Liliana Quintanar, Jaime Santoyo-Salazar, Armando J Espadas-Álvarez, Daniel Martínez-Fong, Elizabeth García-García
Neurotensin (NTS)-polyplex is a nanoparticle system for targeted gene delivery that holds great promise for treatment of Parkinson's disease and various types of cancer. However, the high instability in aqueous suspension of NTS-polyplex nanoparticles is a major limitation for their widespread clinical use. To overcome this obstacle, we developed a clinical formulation and a lyophilization process for NTS-polyplex nanoparticles. The reconstituted samples were compared with fresh preparations by using transmission electron microscopy, dynamic light scattering, electrophoretic mobility, circular dichroism and transfection assays in vitro and in vivo...
January 3, 2018: Pharmaceutics
Laura E Schroeder, Gina M Leinninger
The peptide neurotensin (Nts) was discovered within the brain over 40 years ago and is implicated in regulating analgesia, body temperature, blood pressure, locomotor activity and feeding. Recent evidence suggests, however, that these disparate processes may be controlled via specific populations of Nts neurons and receptors. The neuronal mediators of Nts anorectic action are now beginning to be understood, and, as such, modulating specific Nts pathways might be useful in treating feeding and body weight disorders...
December 27, 2017: Biochimica et Biophysica Acta
Teresa Auguet, Gemma Aragonès, Alba Berlanga, Salomé Martínez, Fàtima Sabench, Carmen Aguilar, Beatriz Villar, Joan Josep Sirvent, Daniel Del Castillo, Cristóbal Richart
OBJECTIVE: This study was performed to investigate neurotensin plasma levels in patients with nonalcoholic fatty liver disease (NAFLD) associated with severe obesity. METHODS: The plasma levels of neurotensin in 20 women with normal weight and 51 women with morbid obesity (MO) were measured, and women were subclassified according to their hepatic histology as having MO without NAFLD (n = 18) or MO with NAFLD (n = 33). The NAFLD group included 15 women with simple steatosis (SS) and 18 women with nonalcoholic steatohepatitis (NASH)...
December 25, 2017: Obesity
Hillary L Woodworth, Bethany G Beekly, Hannah M Batchelor, Raluca Bugescu, Patricia Perez-Bonilla, Laura E Schroeder, Gina M Leinninger
The central mechanism by which neurotensin (Nts) potentiates weight loss has remained elusive. We leveraged chemogenetics to reveal that Nts-expressing neurons of the lateral hypothalamic area (LHA) promote weight loss in mice by increasing volitional activity and restraining food intake. Intriguingly, these dual weight loss behaviors are mediated by distinct signaling pathways: Nts action via NtsR1 is essential for the anorectic effect of the LHA Nts circuit, but not for regulation of locomotor or drinking behavior...
December 12, 2017: Cell Reports
Xiao Meng, Junjie Hu, Zhicong Chao, Ying Liu, Huangxian Ju, Quan Cheng
Sample desalting and concentrating is a crucial step prior to MALDI-MS analysis. Current sample pretreatment approaches require tedious fabrication and operation procedures, which are unamenable to high-throughput analysis and also result in sample loss. Here we report the development of a smart MALDI substrate for on-plate desalting, enrichment, and direct MS analysis of protein digests based on thermo-responsive, hydrophilic/hydrophobic transition of surface grafted poly(N-isopropylacrylamide) (PNIPAM) microarrays...
December 14, 2017: ACS Applied Materials & Interfaces
Katarzyna Kaczyńska, Dominika Zając, Piotr Wojciechowski, Ewelina Kogut, Małgorzata Szereda-Przestaszewska
Regulatory neuropeptides control and regulate breathing in physiological and pathophysiological conditions. While they have been identified in the neurons of major respiratory areas, they can be active not only at the central level, but also at the periphery via chemoreceptors, vagal afferents, or locally within lungs and airways. Some neuropeptides, such as leptin or substance P, are respiratory stimulants; others, such as neurotensin, produce variable effects on respiration depending on the site of application...
December 6, 2017: Pulmonary Pharmacology & Therapeutics
Rune E Kuhre, Charlotte B Christiansen, Monika Y Saltiel, Nicolai J Wewer Albrechtsen, Jens J Holst
Ingested glucose powerfully stimulates the secretion of appetite- and metabolism-regulating peptide hormones from the gut - including glucagon-like peptide-1 (GLP-1), neurotensin (NT), and polypeptide YY (PYY). However, the regional origin of these secretions after glucose stimulation is not well characterized, and it remains uncertain how their secretion is related to glucose absorption. We isolated and perfused either the upper (USI) or the lower (LSI) small intestine or the colon from rats and investigated concomitant glucose absorption and secretory profiles of GLP-1, NT, and PYY In the USI and LSI luminal glucose (20%, w/v) increased GLP-1 and NT secretion five to eightfold compared to basal secretion...
December 2017: Physiological Reports
Pedro F Teixeira, Geoffrey Masuyer, Catarina M Pinho, Rui M M Branca, Beata Kmiec, Cecilia Wallin, Sebastian K T S Wärmländer, Ronnie P-A Berntsson, Maria Ankarcrona, Astrid Gräslund, Janne Lehtiö, Pål Stenmark, Elzbieta Glaser
Proteolysis plays an important role in mitochondrial biogenesis, from the processing of newly imported precursor proteins to the degradation of mitochondrial targeting peptides. Disruption of peptide degradation activity in yeast, plant and mammalian mitochondria is known to have deleterious consequences for organism physiology, highlighting the important role of mitochondrial peptidases. In the present work, we show that the human mitochondrial peptidase neurolysin (hNLN) can degrade mitochondrial presequence peptides as well as other fragments up to 19 amino acids long...
November 25, 2017: Journal of Molecular Biology
Arzu Uyar, Vardan Karamyan, Alex Dickson
Crystal structures of neurolysin, a zinc metallopeptidase, do not show a significant conformational change upon the binding of an allosteric inhibitor. Neurolysin has a deep channel where it hydrolyzes a short neuropeptide neurotensin to create inactive fragments and thus controls its level in the tissue. Neurolysin is of interest as a therapeutic target since changes in neurotensin level have been implicated in cardiovascular disorders, neurological disorders and cancer, and inhibitors of neurolysin have been developed...
November 27, 2017: Journal of Chemical Theory and Computation
David Reyes-Corona, Nallely Vázquez-Hernández, Lourdes Escobedo, Carlos E Orozco-Barrios, Jose Ayala-Davila, Mario Gil Moreno, Miriam E Amaro-Lara, Yazmin M Flores-Martinez, Armando J Espadas-Alvarez, Manuel A Fernandez-Parrilla, Juan A Gonzalez-Barrios, M E Gutierrez-Castillo, Ignacio González-Burgos, Daniel Martinez-Fong
The structural effect of neurturin (NRTN) on the nigrostriatal dopaminergic system in animals remains unknown, although NRTN has been shown to be effective in Parkinson's disease animal models. Herein, we aimed to demonstrate that NRTN overexpression in dopaminergic neurons stimulates both neurite outgrowths in the nigrostriatal pathway and striatal dendritic spines in aging rats with chronic 6-hydroxydopamine (6-OHDA) lesion. At week 12 after lesion, pTracer-mNRTN-His or pGreenLantern-1 plasmids were intranigrally transfected using the NTS-polyplex nanoparticles system...
2017: PloS One
Nadia Leloup, Philip Lössl, Dimphna H Meijer, Martha Brennich, Albert J R Heck, Dominique M E Thies-Weesie, Bert J C Janssen
Low pH-induced ligand release and receptor recycling are important steps for endocytosis. The transmembrane protein sortilin, a β-propeller containing endocytosis receptor, internalizes a diverse set of ligands with roles in cell differentiation and homeostasis. The molecular mechanisms of pH-mediated ligand release and sortilin recycling are unresolved. Here we present crystal structures that show the sortilin luminal segment (s-sortilin) undergoes a conformational change and dimerizes at low pH. The conformational change, within all three sortilin luminal domains, provides an altered surface and the dimers sterically shield a large interface while bringing the two s-sortilin C-termini into close proximity...
November 22, 2017: Nature Communications
G A Gerbrand Zoet, B B Bas van Rijn, M Miriam Rehfeldt, A Arie Franx, A H E M Angela Maas
OBJECTIVE: Women are at increased risk of developing cardiovascular disease (CVD) after preeclampsia. Proneurotensin 1-117 (pro-NT) and prorelaxin 2 connecting peptide (pro-RLX2) have recently emerged as potential biomarkers for CVD risk in women. We assessed pro-NT and pro-RLX2 levels in women with and without a history of preeclampsia. STUDY DESIGN: 339 women with a history of early-onset preeclampsia and 327 women with an uncomplicated pregnancy underwent cardiovascular screening 10 years after delivery (the Preeclampsia Risk EValuation in FEMales (PREVFEM) cohort)...
December 2017: Maturitas
Hiroki Hashi, Yasuyuki Nakamura, Jun Ishii, Akihiko Kondo
Neurotensin receptor type 1 (NTSR1), a member of the G-protein-coupled receptor (GPCR) family, is naturally activated by binding of a neurotensin peptide, leading to a variety of physiological effects. The budding yeast Saccharomyces cerevisiae is a proven host organism for assaying the agonistic activation of human GPCRs. Previous studies showed that yeast cells can functionally express human NTSR1 receptor, permitting the detection of neurotensin-promoted signaling using a ZsGreen fluorescent reporter gene...
November 13, 2017: Biotechnology Journal
Roxanna Zakeri, Rachel L Batterham
PURPOSE OF REVIEW: Reduced energy intake, resulting from favourable changes in eating behaviour, is the predominant driver of weight loss following bariatric surgery. Here we review the most recent studies examining the impact of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy, the two most common bariatric procedures, upon eating behaviour and the suggested underlying biological mechanisms. RECENT FINDINGS: Following RYGB or sleeve gastrectomy, most people report subjective changes in appetite, taste and food preference, with decreased high-fat preference most commonly reported...
November 7, 2017: Current Opinion in Endocrinology, Diabetes, and Obesity
Simone Maschauer, Olaf Prante
The neurotensin receptors are overexpressed in various tumor types, especially in highly progressive pancreatic tumors. As this cancer has a poor 5-year survival prognosis, there is an urgent need to improve early diagnosis and treatment strategies. This review article provides an overview of the latest developments in radiopharmaceuticals for neurotensin receptor-positive tumors, including peptidic and non-peptidic radiopharmaceuticals, not only for SPECT and PET but also for endoradiotherapy.
November 7, 2017: Journal of Labelled Compounds & Radiopharmaceuticals
Giuseppe Riezzo, Guglielmina Chimienti, Caterina Clemente, Benedetta D'Attoma, Antonella Orlando, Caterina Mammone Rinaldi, Francesco Russo
PURPOSE: To investigate whether pathophysiological differences exist among healthy controls (HC) and patients with slow and normal transit constipation (STC and NTC), we evaluated (1) gastrointestinal (GI) symptoms using validated questionnaires; (2) circulating concentrations of neurotensin, motilin, corticotrophin-releasing factor (CRF), and somatostatin; and (3) possible differences in frequency distribution of the neurotensin rs1800832 A/G and Neurotensin Receptor 1 rs6090453 C/G SNPs...
2017: BioMed Research International
Ibrahim Malik, Søren Christensen, Jeffrey B Stavenhagen, Gunnar P H Dietz
Sortilin was first identified based on its activity as part of intracellular protein sorting machinery. Recently, it was discovered that sortilin also acts as a cell surface receptor for the propeptide form of nerve growth factor (proNGF), progranulin, and neurotensin. The interaction of sortilin to these neurotrophic ligands is linked to diseases of the nervous system that lead to neurodegeneration and neuropathic pain. Blocking of the interaction of sortilin to these ligands may prevent or slow the progress of these nervous system disorders...
October 24, 2017: Cellular and Molecular Neurobiology
Hualiang Xiao, Ying Zeng, Qiushi Wang, Shirong Wei, Xiangfeng Zhu
BACKGROUND/AIMS: Neurotensin (NTS), an intestinal hormone, is profoundly implicated in cancer progression through binding its primary receptor NTSR1. The conserved Wnt/β-Catenin pathway regulates cell proliferation and differentiation via activation of the β-catenin/T-cell factor (TCF) complex and subsequent modulation of a set of target genes. In this study, we aimed to uncover the potential connection between NTS/NTSR1 signaling and Wnt/β-Catenin pathway. METHODS: Genetic silencing, pharmacological inhibition and gain-of-function studies as well as bioinformatic analysis were performed to uncover the link between NTS/ NTSR1 signaling and Wnt/β-Catenin pathway...
October 24, 2017: Cellular Physiology and Biochemistry
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