Journal: International Journal of Molecular Sciences
Article Title: Oxidative DNA Damage, Inflammatory Signature, and Altered Erythrocytes Properties in Diamond-Blackfan Anemia
doi: 10.3390/ijms21249652
Figure Lengend Snippet: Interplay of deregulated pathways in Diamond-Blackfan anemia (DBA). Ribosomal protein (RP)-haploinsufficiency induces ribosomal stress leading to the activation of p53, induction of inflammatory signaling, and oxidative stress/damage. Multiple feedback loops between DNA damage response (DDR)/p53 activation and inflammatory cytokine production and between p53 activation and cell fate decisions (apoptosis/senescence) is expected. Similarly, a crosstalk between inflammatory cytokines and oxidative damage is presumed. Cells with activated DDR/p53 and exposed to inflammation and reactive oxygen species (ROS) may undergo senescence or apoptosis depending on the cellular context and DDR signaling thresholds. Damaged/senescent cells may further reinforce inflammatory cytokine production. The detailed hierarchical nature of cooperation between each deregulated pathway in DBA pathobiology needs to be defined.
Article Snippet: For the first seven days, 1 × 10 6 /mL MNCs were cultured in StemPro™-34 SFM medium (ThermoFisher Scientific, Waltham, MA, USA) containing L-glutamine (2 mM, ThermoFisher Scientific, Waltham, MA, USA), 1X cytokine cocktail StemSpan™ CC110 (StemCell Technologies, Vancouver, BC, Canada), recombinant human erythropoietin (EPO, 2 U/mL; StemCell Technologies, Vancouver, BC, Canada), and the synthetic glucocorticoid dexamethasone (Dex, 1 µM; Sigma-Aldrich, Darmstadt, Germany).
Techniques: Activation Assay