title: Ghrelin binding to serum albumin and its biological impact.
abstract: Ghrelin is an octanoylated peptide hormone that plays a key role in the regulation of the body weight and glucose homeostasis. In plasma, ghrelin circulates bound to larger proteins whose identities are partially established. Here, we used size exclusion chromatography, mass spectrometry and isothermal titration microcalorimetry to show that ghrelin interacts with serum albumin. Furthermore, we found that such interaction displays an estimated dissociation constant (KD) in the micromolar range and involves albumin fatty-acid binding sites as well as the octanoyl moiety of ghrelin. Notably, albumin-ghrelin interaction reduces the spontaneous deacylation of the hormone. Both in vitro experiments-assessing ghrelin ability to inhibit calcium channels-and in vivo studies-evaluating ghrelin orexigenic effects-indicate that the binding to albumin affects the bioactivity of the hormone. In conclusion, our results suggest that ghrelin binds to serum albumin and that this interaction impacts on the biological activity of the hormone.
authors.affiliation: Instituto Multidisciplinario de Biología Celular, Conicet, Argentina.
authors.forename: Daniela
authors.initials: D
authors.lastname: Lufrano
authors.affiliation: Instituto Multidisciplinario de Biología Celular, Conicet, Argentina; Servei de Proteòmica i Biologia Estructural, Universitat Autònoma de Barcelona, Spain.
authors.forename: Sebastián A
authors.initials: SA
authors.lastname: Trejo
authors.affiliation: Instituto Multidisciplinario de Biología Celular, Conicet, Argentina.
authors.forename: Ramiro E
authors.initials: RE
authors.lastname: Llovera
authors.affiliation: Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Argentina.
authors.forename: Mariano
authors.initials: M
authors.lastname: Salgueiro
authors.affiliation: Instituto Multidisciplinario de Biología Celular, Conicet, Argentina.
authors.forename: Gimena
authors.initials: G
authors.lastname: Fernandez
authors.affiliation: Instituto Multidisciplinario de Biología Celular, Conicet, Argentina.
authors.forename: Valentina
authors.initials: V
authors.lastname: Martínez Damonte
authors.affiliation: Instituto de Química y Fisicoquímica Biológicas, Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
authors.forename: F Luis
authors.initials: FL
authors.lastname: González Flecha
authors.affiliation: Instituto Multidisciplinario de Biología Celular, Conicet, Argentina.
authors.forename: Jesica
authors.initials: J
authors.lastname: Raingo
authors.affiliation: Instituto Multidisciplinario de Biología Celular, Conicet, Argentina; Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Argentina.
authors.forename: Mario R
authors.initials: MR
authors.lastname: Ermácora
authors.affiliation: Instituto Multidisciplinario de Biología Celular, Conicet, Argentina. Electronic address: mperello@imbice.gov.ar.
authors.forename: Mario
authors.initials: M
authors.lastname: Perelló
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002151:Calorimetry; D002850:Chromatography, Gel; D054439:Ghrelin / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D051379:Mice; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D054439:Ghrelin; D012709:Serum Albumin
keywords: Ghrelin; Hormone; Protein-protein interaction; Serum albumin; Transport