Thymosin β4 Is an Endogenous Iron Chelator and Molecular Switcher of Ferroptosis
Lachowicz JI, Pichiri G, Piludu M, Fais S, Orrù G, Congiu T, Piras M, Faa G, Fanni D, Torre GD, Lopez X, Chandra K, Szczepski K, Jaremko L, Ghosh M, Emwas AH, Castagnola M, Jaremko M, Hannappel E, Coni P (2022)
Publication Type: Journal article
Publication year: 2022
Journal
Book Volume: 23
Article Number: 551
Journal Issue: 1
DOI: 10.3390/ijms23010551
Abstract
Thymosin β4 (Tβ4) was extracted forty years agofrom calf thymus. Since then, it has been identified as a G‐actin binding protein involved in blood clotting, tissue regeneration, angiogenesis, and anti‐inflammatory processes. Tβ4 has also been implicated in tumor metastasis and neuro-degeneration. However, the precise roles and mechanism(s) of action of Tβ4 in these processes re-main largely unknown, with the binding of the G‐actin protein being insufficient to explain these multi‐actions. Here we identify for the first time the important role of Tβ4 mechanism in ferroptosis, an iron‐dependent form of cell death, which leads to neurodegeneration and somehow protects cancer cells against cell death. Specifically, we demonstrate four iron2+ and iron3+ binding regions along the peptide and show that the presence of Tβ4 in cell growing medium inhibits erastin and glutamate‐induced ferroptosis in the macrophage cell line. Moreover, Tβ4 increases the expression of oxidative stress‐related genes, namely BAX, hem oxygenase‐1, heat shock protein 70 and thiore-doxin reductase 1, which are downregulated during ferroptosis. We state the hypothesis that Tβ4 is an endogenous iron chelator and take part in iron homeostasis in the ferroptosis process. We discuss the literature data of parallel involvement of Tβ4 and ferroptosis in different human pathologies, mainly cancer and neurodegeneration. Our findings confronted with literature data show that con-trolled Tβ4 release could command on/off switching of ferroptosis and may provide novel therapeutic opportunities in cancer and tissue degeneration pathologies.
Authors with CRIS profile
Involved external institutions
Università degli Studi di Cagliari
Italy (IT)
University of Basque Country / Universidad del Pais Vasco (UPV) / Euskal Herriko Unibersitatea (EHU)
Spain (ES)
King Abdullah University of Science and Technology (KAUST) / جامعة الملك عبد الله للعلوم و التقنية
Saudi Arabia (SA)
Consiglio Nazionale delle Ricerche (CNR) / National Research Council of Italy
Italy (IT)
Italy (IT)
University of Basque Country / Universidad del Pais Vasco (UPV) / Euskal Herriko Unibersitatea (EHU)
Spain (ES)
King Abdullah University of Science and Technology (KAUST) / جامعة الملك عبد الله للعلوم و التقنية
Saudi Arabia (SA)
Consiglio Nazionale delle Ricerche (CNR) / National Research Council of Italy
Italy (IT)
How to cite
APA:
Lachowicz, J.I., Pichiri, G., Piludu, M., Fais, S., Orrù, G., Congiu, T.,... Coni, P. (2022). Thymosin β4 Is an Endogenous Iron Chelator and Molecular Switcher of Ferroptosis. International Journal of Molecular Sciences, 23(1). https://dx.doi.org/10.3390/ijms23010551
MLA:
Lachowicz, Joanna I., et al. "Thymosin β4 Is an Endogenous Iron Chelator and Molecular Switcher of Ferroptosis." International Journal of Molecular Sciences 23.1 (2022).
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