The influence of redox modulation on hypoxic endothelial cell metabolic and proteomic profiles through a small thiol-based compound tuning glutathione and thioredoxin systems

Bruschi, Michela
Biancucci, Federica
Masini, Sofia
Piacente, Francesco
Ligi, Daniela
Bartoccini, Francesca
Antonelli, Antonella
Mannello, Ferdinando
Bruzzone, Santina
Menotta, Michele
Fraternale, Alessandra
Magnani, Mauro

Publication date

January 2023

DOI

10.1002/biof.1988

Abstract

: Reduction in oxygen levels is a key feature in the physiology of the bone marrow (BM) niche where hematopoiesis occurs. The BM niche is a highly vascularized tissue and endothelial cells (ECs) support and regulate blood cell formation from hematopoietic stem cells (HSCs). While in vivo studies are limited, ECs when cultured in vitro at low O2 (<5%), fail to support functional HSC maintenance due to oxidative environment. Therefore, changes in EC redox status induced by antioxidant molecules may lead to alterations in the cellular response to hypoxia likely favoring HSC self-renewal. To evaluate the impact of redox regulation, HUVEC, exposed for 1, 6, and 24 h to 3% O2 were treated with N-(N-acetyl-l-cysteinyl)-S-acetylcysteamine (I-152). ...