Oxidative DNA Damage, Inflammatory Signature, and Altered Erythrocytes Properties in Diamond-Blackfan Anemia

0538165 - ÚMG 2021 RIV CH eng J - Článek v odborném periodiku
Kapralova, K. - Jahoda, O. - Koralkova, P. - Gursky, J. - Láníková, Lucie - Pospíšilová, D. - Divoky, V. - Horvathova, M.
Oxidative DNA Damage, Inflammatory Signature, and Altered Erythrocytes Properties in Diamond-Blackfan Anemia.
International Journal of Molecular Sciences. Roč. 21, č. 24 (2020), č. článku 9652. E-ISSN 1422-0067
Institucionální podpora: RVO:68378050
Klíčová slova: Diamond-Blackfan anemia * reactive oxygen species * 8-oxoguanine * DNA damage response * inflammatory cytokines * erythrocyte lifespan
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 5.924, rok: 2020
Způsob publikování: Open access
https://www.mdpi.com/1422-0067/21/24/9652

Molecular pathophysiology of Diamond-Blackfan anemia (DBA) involves disrupted erythroid-lineage proliferation, differentiation and apoptosis, with the activation of p53 considered as a key component. Recently, oxidative stress was proposed to play an important role in DBA pathophysiology as well. CRISPR/Cas9-created Rpl5- and Rps19-deficient murine erythroleukemia (MEL) cells and DBA patients' samples were used to evaluate proinflammatory cytokines, oxidative stress, DNA damage and DNA damage response. We demonstrated that the antioxidant defense capacity of Rp-mutant cells is insufficient to meet the greater reactive oxygen species (ROS) production which leads to oxidative DNA damage, cellular senescence and activation of DNA damage response signaling in the developing erythroblasts and altered characteristics of mature erythrocytes. We also showed that the disturbed balance between ROS formation and antioxidant defense is accompanied by the upregulation of proinflammatory cytokines. Finally, the alterations detected in the membrane of DBA erythrocytes may cause their enhanced recognition and destruction by reticuloendothelial macrophages, especially during infections. We propose that the extent of oxidative stress and the ability to activate antioxidant defense systems may contribute to high heterogeneity of clinical symptoms and response to therapy observed in DBA patients.
Trvalý link: http://hdl.handle.net/11104/0315987