title: Klotho Prevents NFκB Translocation and Protects Endothelial Cell From Senescence Induced by Uremia.
abstract: In patients with renal disease, uremia raises oxidative stress and senescence in endothelial cells, which can lead to endothelial dysfunction and cardiovascular disease. Klotho protein is a β-glucuronidase capable of hydrolyzing steroid β-glucuronides. This protein is recognized as an antiaging gene, that modulate both stress-induced senescence and functional response. The aim of the study was to investigate how senescence and oxidative stress induced by uremia in endothelial cells affects Klotho expression and whether intra or extracellular Klotho has effects on the response of these cells. Senescence and oxidative stress was obtained by exposure to uremic serum. Telomere length, the enzyme β-galactosidase, and oxidative stress were studied by flow cytometry. Nuclear factor kappa B activity was determined by electrophoretic mobility shift assay. The expression of Klotho decreased with the uremia and preceded the manifestations of cell aging. Levels of intracellular Klotho decreases associated to endothelial senescence, and exogenous Klotho prevents cellular senescence by inhibiting the increase in oxidative stress induced by uremia and diminished the nuclear factor kappa B-DNA binding ability.
authors.affiliation: Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba, Hospital Universitaro Reina Sofía, Córdoba, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: Buendía
authors.affiliation: Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba, Hospital Universitaro Reina Sofía, Córdoba, Spain. julia.carracedo.exts@juntadeandalucia.es.
authors.forename: Julia
authors.initials: J
authors.lastname: Carracedo
authors.affiliation: Nephrology Unit, Hospital Universitaro Reina Sofía, Córdoba, Spain.
authors.forename: Sagrario
authors.initials: S
authors.lastname: Soriano
authors.affiliation: Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba, Hospital Universitaro Reina Sofía, Córdoba, Spain.
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Madueño
authors.affiliation: REDinREN, Servicio de Nefrología, Fundación para la Investigación Biomédica del Hospital Universitario La Paz, Instituto de Salud Carlos III, Fondos FEDER, Madrid, Spain. Unidad de Diálisis, Fundación Jiménez Díaz, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
authors.forename: Alejandro
authors.initials: A
authors.lastname: Martín-Malo
authors.forename: Pedro
authors.initials: P
authors.lastname: Aljama
authors.affiliation: REDinREN, Servicio de Nefrología, Fundación para la Investigación Biomédica del Hospital Universitario La Paz, Instituto de Salud Carlos III, Fondos FEDER, Madrid, Spain. Physiology Department, Alcala de Henares University, Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Ramírez
mesh_terms: D000368:Aged; D002460:Cell Line; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D005966:Glucuronidase / Q000494:pharmacology*; D006801:Humans; D007677:Kidney Function Tests; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D016615:Telomere / Q000648:ultrastructure; D014511:Uremia / Q000378:metabolism* / Q000503:physiopathology*
chemical_list: D016328:NF-kappa B; D005966:Glucuronidase; D000090265:Klotho Proteins
keywords: Klotho; NFκB; Senescence; Uremic serum