Journalartikel
Autorenliste: Czarnecka-Herok, Joanna; Zhu, Kexin; Flaman, Jean -Michel; Goehrig, Delphine; Vernier, Mathieu; Makulyte, Gabriela; Lamboux, Aline; Dragic, Helena; Rhinn, Muriel; Medard, Jean -Jacques; Faury, Gilles; Bertolino, Philippe; Balter, Vincent; Debret, Romain; Adnot, Serge; Martin, Nadine; Bernard, David
Jahr der Veröffentlichung: 2024
Zeitschrift: Redox Biology
Bandnummer: 73
ISSN: 2213-2317
Open Access Status: Gold
DOI Link: https://doi.org/10.1016/j.redox.2024.103204
Verlag: Elsevier
Abstract:
The ELN gene encodes tropoelastin which is used to generate elastic fibers that insure proper tissue elasticity. Decreased amounts of elastic fibers and/or accumulation of bioactive products of their cleavage, named elastokines, are thought to contribute to aging. Cellular senescence, characterized by a stable proliferation arrest and by the senescence-associated secretory phenotype (SASP), increases with aging, fostering the onset and progression of age-related diseases and overall aging, and has so far never been linked with elastin. Here, we identified that decrease in ELN either by siRNA in normal human fibroblasts or by knockout in mouse embryonic fibroblasts results in premature senescence. Surprisingly this effect is independent of elastic fiber degradation or elastokines production, but it relies on the rapid increase in HMOX1 after ELN downregulation. Moreover, the induction of HMOX1 depends on p53 and NRF2 transcription factors, and leads to an increase in iron, further mediating ELN downregulation-induced senescence. Screening of iron-dependent DNA and histones demethylases revealed a role for histone PHF8 demethylase in mediating ELN downregulation-induced senescence. Collectively, these results unveil a role for ELN in protecting cells from cellular senescence through a noncanonical mechanism involving a ROS/HMOX1/iron accumulation/PHF8 histone demethylase pathway reprogramming gene expression towards a senescence program.
Zitierstile
Harvard-Zitierstil: Czarnecka-Herok, J., Zhu, K., Flaman, J., Goehrig, D., Vernier, M., Makulyte, G., et al. (2024) A non-canonical role of ELN protects from cellular senescence by limiting iron-dependent regulation of gene expression, Redox Biology, 73, Article 103204. https://doi.org/10.1016/j.redox.2024.103204
APA-Zitierstil: Czarnecka-Herok, J., Zhu, K., Flaman, J., Goehrig, D., Vernier, M., Makulyte, G., Lamboux, A., Dragic, H., Rhinn, M., Medard, J., Faury, G., Bertolino, P., Balter, V., Debret, R., Adnot, S., Martin, N., & Bernard, D. (2024). A non-canonical role of ELN protects from cellular senescence by limiting iron-dependent regulation of gene expression. Redox Biology. 73, Article 103204. https://doi.org/10.1016/j.redox.2024.103204
Schlagwörter
CELLULAR SENESCENCE; DEMETHYLASE JMJD3 CONTRIBUTES; ELASTIN-DERIVED PEPTIDES; ELN; HMOX1; PHF8
