Uncoupling of Elastin Complex Receptor during In Vitro Aging Is Related to Modifications in Its Intrinsic Sialidase Activity and the Subsequent Lactosylceramide Production

PLoS One. 2015 Jun 18;10(6):e0129994. doi: 10.1371/journal.pone.0129994. eCollection 2015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging
  • Antigens, CD / metabolism*
  • Cells, Cultured
  • Cellular Senescence*
  • Elastin / metabolism*
  • Enzyme Activation
  • Fibroblasts / cytology
  • Fibroblasts / metabolism*
  • Gene Expression Regulation
  • Humans
  • Lactosylceramides / metabolism*
  • Neuraminidase / metabolism*
  • Receptors, Cell Surface / metabolism*

Substances

  • Antigens, CD
  • Lactosylceramides
  • Receptors, Cell Surface
  • elastin-binding proteins
  • CDw17 antigen
  • Elastin
  • Neuraminidase

Grants and funding

This work was supported by grants from the CNRS (Centre National de la Recherche Scientifique) and the Ministère de l’Enseignement Supérieur et de la Recherche. Amandine Scandolera is a fellow of the Ministère de l’Enseignement Supérieur et de la Recherche. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.