Gender disparity in susceptibility to Oxidative stress and apoptosis induced by autoantibodies specific to RLIP76 in vascular cells

Paola Matarrese, Tania Colasanti, Barbara Ascione, Paola Margutti, Flavia Franconi, Cristiano Alessandri, Fabrizio Conti, Valeria Riccieri, Giuseppe Rosano, Elena Ortona, Walter Malorni

Research output: Contribution to journalArticle

Abstract

Aim: Ral-binding protein 1 (RLIP76) is a cell surface protein that catalyzes the extrusion from the cell of reduced glutathione (GSH) conjugates. We recently demonstrated the presence of serum antibodies to RLIP76 (aaRLIP76) in patients with immune-mediated diseases characterized by vascular dysfunction. The aim of this work was to analyze the possible implication of gender in this issue, investigating the effects of aaRLIP76 in rat vascular smooth muscle cells and human endothelial cells from males and females. Results: We observed that, after aaRLIP76 treatment, vascular cells from females showed a significantly higher susceptibility to the disturbance of intracellular redox balance, in terms of H2O2 and O2 production, 4-hydroxy-t-2,3-nonenal and GSH levels, C-Jun NH2 kinase signaling activation, and apoptosis in comparison with cells from males. Interestingly, under mild oxidative stress (H2O2 30μm for 30min), these sex-associated differences became significantly more pronounced. Experiments carried out in the presence of sex hormones in the culture medium clearly suggested that estrogens could significantly increase the susceptibility of cells from females to the effects of aaRLIP76, whereas cells from males appeared unaffected. Innovation: These results open a new perspective in the gender-dependent pathogenic mechanisms of autoimmune diseases characterized by vascular dysfunction. Conclusions: Altogether these results suggest that the impairment of RLIP76 by aaRLIP76 can play a role in the damage of vascular cells from females, contributing to the gender-associated pathogenesis of immune-mediated vascular diseases.

Original languageEnglish
Pages (from-to)2825-2836
Number of pages12
JournalAntioxidants and Redox Signaling
Volume15
Issue number11
DOIs
Publication statusPublished - Dec 1 2011

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Physiology
  • Clinical Biochemistry

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    Matarrese, P., Colasanti, T., Ascione, B., Margutti, P., Franconi, F., Alessandri, C., Conti, F., Riccieri, V., Rosano, G., Ortona, E., & Malorni, W. (2011). Gender disparity in susceptibility to Oxidative stress and apoptosis induced by autoantibodies specific to RLIP76 in vascular cells. Antioxidants and Redox Signaling, 15(11), 2825-2836. https://doi.org/10.1089/ars.2011.3942