Kinetic Redox Shotgun Proteomics Reveals Specific Lipopolysaccharide Effects on Intestinal Epithelial Cells, Mitigated by a Mn Superoxide Dismutase Mimic
Overproduction of reactive oxygen species and antioxidant superoxide dismutases (SOD1, SOD2) dysregulation contribute to chronic inflammation such as generated in inflammatory bowel diseases (IBD). A kinetic redox shotgun proteomic strategy (OcSILAC for Oxidized cysteine Stable Isotope Labelling by Amino acids in Cell culture) was used to explore the lipopolysaccharide (LPS) effects including LPS-induced oxidation and inflammation cascades on a dedicated intestinal epithelial cell line (HT29-MD2) together with the potential mitigating role of a Mn-based SOD-mimic Mn1. While LPS induced transient oxidative damages at early times (15 min), cells incubated with Mn1 showed, in this time frame, a significantly reduced cysteine oxidation, highlighting Mn1 antioxidant properties. Over time, cysteine oxidation of LPS-treated cells was counteracted by an overexpression of antioxidant proteins (SOD1, NQO1) and a late (6 h) preponderant increase in SOD2 level. Mn1, when co-incubated with LPS, attenuated the level of most LPS-modified proteins, that is, proteins involved in the inflammatory response. Our results highlight Mn1 as a potentially effective antioxidant and anti-inflammatory agent to consider in the treatment of IBD, as well as a useful tool for exploring the interconnection between oxidative stress and inflammation.
Authors
- Émilie Mathieu (ORCID: https://orcid.org/0000-0002-9313-8679)
- Shakir Shakir
- Joëlle Vinh (ORCID: https://orcid.org/0000-0001-7184-2668)
- Giovanni Chiappetta (ORCID: https://orcid.org/0000-0001-8959-2230)
- Samuel Diebolt (ORCID: https://orcid.org/0000-0002-9788-7263)
- Pauline Gehan
- Sylvie Demignot (ORCID: https://orcid.org/0000-0001-7149-1992)
- Elodie Quévrain
- Gabrielle Schanne (ORCID: https://orcid.org/0000-0002-8601-1485)
- Clotilde Policar (ORCID: https://orcid.org/0000-0003-0255-1650)
- Philippe Seksik (ORCID: https://orcid.org/0000-0003-3596-9893)
- Martha Zoumpoulaki (ORCID: https://orcid.org/0000-0002-5276-9626)
- Nicolas Delsuc (ORCID: https://orcid.org/0000-0001-5570-8311)
- Jean Bouvet
Institutions
- Centre National de la Recherche Scientifique (FR)
- Chimie ParisTech - PSL (FR)
- Inserm (FR)
- École Pratique des Hautes Études (FR)
- Université Paris Sciences et Lettres (FR)
- École Normale Supérieure - PSL (FR)
- Sorbonne Université (FR)
- Centre National pour la Recherche Scientifique et Technique (CNRST) (MA)
- École Normale Supérieure (BI)
- Centre de Recherche Saint-Antoine (FR)
- École Normale Supérieure d'Abidjan (CI)
- Protéomique, Réponse Inflammatoire et Spectrométrie de Masse (FR)
- ESPCI Paris (FR)
Publication Details
- Journal
- Angewandte Chemie International Edition
- Published
- 2025-03-11
- DOI
- https://doi.org/10.1002/anie.202422644
- Citations
- 2
- Primary Topic
- Molecular Biology Techniques and Applications
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- Agence Nationale de la Recherche
- Indo-French Centre for the Promotion of Advanced Research
- Centre National de la Recherche Scientifique
- Sorbonne Université