title: Uncoupling of Elastin Complex Receptor during In Vitro Aging Is Related to Modifications in Its Intrinsic Sialidase Activity and the Subsequent Lactosylceramide Production.
abstract: Degradation of elastin leads to the production of elastin-derived peptides (EDP), which exhibit several biological effects, such as cell proliferation or protease secretion. Binding of EDP on the elastin receptor complex (ERC) triggers lactosylceramide (LacCer) production and ERK1/2 activation following ERC Neu-1 subunit activation. The ability for ERC to transduce signals is lost during aging, but the mechanism involved is still unknown. In this study, we characterized an in vitro model of aging by subculturing human dermal fibroblasts. This model was used to understand the loss of EDP biological activities during aging. Our results show that ERC uncoupling does not rely on Neu-1 or PPCA mRNA or protein level changes. Furthermore, we observe that the membrane targeting of these subunits is not affected with aging. However, we evidence that Neu-1 activity and LacCer production are altered. Basal Neu-1 catalytic activity is strongly increased in aged cells. Consequently, EDP fail to promote Neu-1 catalytic activity and LacCer production in these cells. In conclusion, we propose, for the first time, an explanation for ERC uncoupling based on the age-related alterations of Neu-1 activity and LacCer production that may explain the loss of EDP-mediated effects occurring during aging.
authors.affiliation: Laboratoire Signalisation et Récepteurs Matriciels (SiRMa), UMR CNRS/URCA 7369, SFR CAP Santé, Université de Reims Champagne Ardenne, Faculté des Sciences, Reims, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Scandolera
authors.affiliation: Laboratoire Signalisation et Récepteurs Matriciels (SiRMa), UMR CNRS/URCA 7369, SFR CAP Santé, Université de Reims Champagne Ardenne, Faculté des Sciences, Reims, France.
authors.forename: Fanja
authors.initials: F
authors.lastname: Rabenoelina
authors.affiliation: Laboratoire Signalisation et Récepteurs Matriciels (SiRMa), UMR CNRS/URCA 7369, SFR CAP Santé, Université de Reims Champagne Ardenne, Faculté des Sciences, Reims, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Chaintreuil
authors.affiliation: Laboratoire Signalisation et Récepteurs Matriciels (SiRMa), UMR CNRS/URCA 7369, SFR CAP Santé, Université de Reims Champagne Ardenne, Faculté des Sciences, Reims, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Rusciani
authors.affiliation: Laboratoire Signalisation et Récepteurs Matriciels (SiRMa), UMR CNRS/URCA 7369, SFR CAP Santé, Université de Reims Champagne Ardenne, Faculté des Sciences, Reims, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Maurice
authors.affiliation: Laboratoire Signalisation et Récepteurs Matriciels (SiRMa), UMR CNRS/URCA 7369, SFR CAP Santé, Université de Reims Champagne Ardenne, Faculté des Sciences, Reims, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Blaise
authors.affiliation: Laboratoire Signalisation et Récepteurs Matriciels (SiRMa), UMR CNRS/URCA 7369, SFR CAP Santé, Université de Reims Champagne Ardenne, Faculté des Sciences, Reims, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Romier-Crouzet
authors.affiliation: Laboratoire Signalisation et Récepteurs Matriciels (SiRMa), UMR CNRS/URCA 7369, SFR CAP Santé, Université de Reims Champagne Ardenne, Faculté des Sciences, Reims, France.
authors.forename: Hassan
authors.initials: H
authors.lastname: El Btaouri
authors.affiliation: Laboratoire Signalisation et Récepteurs Matriciels (SiRMa), UMR CNRS/URCA 7369, SFR CAP Santé, Université de Reims Champagne Ardenne, Faculté des Sciences, Reims, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Martiny
authors.affiliation: Laboratoire Signalisation et Récepteurs Matriciels (SiRMa), UMR CNRS/URCA 7369, SFR CAP Santé, Université de Reims Champagne Ardenne, Faculté des Sciences, Reims, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Debelle
authors.affiliation: Laboratoire Signalisation et Récepteurs Matriciels (SiRMa), UMR CNRS/URCA 7369, SFR CAP Santé, Université de Reims Champagne Ardenne, Faculté des Sciences, Reims, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Duca
mesh_terms: D000375:Aging; D015703:Antigens, CD / Q000378:metabolism*; D002478:Cells, Cultured; D016922:Cellular Senescence; D004549:Elastin / Q000378:metabolism*; D004789:Enzyme Activation; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007790:Lactosylceramides / Q000378:metabolism*; D009439:Neuraminidase / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D007790:Lactosylceramides; D011956:Receptors, Cell Surface; C054901:elastin-binding proteins; C009744:CDw17 antigen; D004549:Elastin; D009439:Neuraminidase