title: Nascent histamine induces α-synuclein and caspase-3 on human cells.
abstract: Histamine (Hia) is the most multifunctional biogenic amine. It is synthetized by histidine decarboxylase (HDC) in a reduced set of mammalian cell types. Mast cells and histaminergic neurons store Hia in specialized organelles until the amine is extruded by exocytosis; however, other immune and cancer cells are able to produce but not store Hia. The intracellular effects of Hia are still not well characterized, in spite of its physiopathological relevance. Multiple functional relationships exist among Hia metabolism/signaling elements and those of other biogenic amines, including growth-related polyamines. Previously, we obtained the first insights for an inhibitory effect of newly synthetized Hia on both growth-related polyamine biosynthesis and cell cycle progression of non-fully differentiated mammalian cells. In this work, we describe progress in this line. HEK293 cells were transfected to express active and inactive versions of GFP-human HDC fusion proteins and, after cell sorting by flow cytometry, the relative expression of a large number of proteins associated with cell signaling were measured using an antibody microarray. Experimental results were analyzed in terms of protein-protein and functional interaction networks. Expression of active HDC induced a cell cycle arrest through the alteration of the levels of several proteins such as cyclin D1, cdk6, cdk7 and cyclin A. Regulation of α-synuclein and caspase-3 was also observed. The analyses provide new clues on the molecular mechanisms underlying the regulatory effects of intracellular newly synthetized Hia on cell proliferation/survival, cell trafficking and protein turnover. This information is especially interesting for emergent and orphan immune and neuroinflammatory diseases.
authors.affiliation: Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga - Andalucia Tech, 29071 Málaga, Spain; CIBER de Enfermedades Raras (CIBERER), 29071 Málaga, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Caro-Astorga
authors.affiliation: Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga - Andalucia Tech, 29071 Málaga, Spain; CIBER de Enfermedades Raras (CIBERER), 29071 Málaga, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Fajardo
authors.affiliation: Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga - Andalucia Tech, 29071 Málaga, Spain; CIBER de Enfermedades Raras (CIBERER), 29071 Málaga, Spain.
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Ruiz-Pérez
authors.affiliation: Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga - Andalucia Tech, 29071 Málaga, Spain; CIBER de Enfermedades Raras (CIBERER), 29071 Málaga, Spain.
authors.forename: Francisca
authors.initials: F
authors.lastname: Sánchez-Jiménez
authors.affiliation: Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga - Andalucia Tech, 29071 Málaga, Spain; CIBER de Enfermedades Raras (CIBERER), 29071 Málaga, Spain. Electronic address: jlurdial@uma.es.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Urdiales
mesh_terms: D053148:Caspase 3 / Q000096:biosynthesis*; D002453:Cell Cycle; D049109:Cell Proliferation / Q000187:drug effects; D057809:HEK293 Cells; D006632:Histamine / Q000502:physiology*; D006640:Histidine Decarboxylase / Q000235:genetics*; D006801:Humans; D015398:Signal Transduction; D014162:Transfection; D051844:alpha-Synuclein / Q000096:biosynthesis*
chemical_list: D051844:alpha-Synuclein; D006632:Histamine; D053148:Caspase 3; D006640:Histidine Decarboxylase
keywords: Apoptosis; Cell cycle; Histamine; Histidine decarboxylase; Synuclein