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dc.contributor.authorLachowicz, Joanna I.
dc.contributor.authorPichiri, Giusi
dc.contributor.authorPiludu, Marco
dc.contributor.authorFais, Sara
dc.contributor.authorOrrù, Germano
dc.contributor.authorCongiu, Terenzio
dc.contributor.authorPiras, Monica
dc.contributor.authorFaa, Gavino
dc.contributor.authorFanni, Daniela
dc.contributor.authorTorre, Gabriele dalla
dc.contributor.authorLopez, Xabier
dc.contributor.authorChandra, Kousik
dc.contributor.authorSzczepski, Kacper
dc.contributor.authorJaremko, Lukasz
dc.contributor.authorGhosh, Mitra
dc.contributor.authorEmwas, Abdul-Hamid M.
dc.contributor.authorMassimo, Castagnola
dc.contributor.authorJaremko, Mariusz
dc.contributor.authorHannappel, Ewald
dc.contributor.authorConi, Pierpaolo
dc.date.accessioned2021-07-12T06:11:46Z
dc.date.available2021-07-12T06:11:46Z
dc.date.issued2021-07-09
dc.identifier.citationLachowicz, J. I., Pichiri, G., Piludu, M., Fais, S., Orrù, G., Congiu, T., … Coni, P. (2021). Thymosin β4 is an Endogenous Iron Chelator and Molecular Switcher of Ferroptosis. doi:10.21203/rs.3.rs-677051/v1
dc.identifier.doi10.21203/rs.3.rs-677051/v1
dc.identifier.urihttp://hdl.handle.net/10754/670123
dc.description.abstractThymosin β4 (Tβ4) was extracted forty years ago $^{1}$ from calf thymus. Since then, it has been identified as a G-actin binding protein involved in blood clothing, tissue regeneration, angiogenesis, and anti-inflammatory processes. Tβ4 has also been implicated in tumor metastasis and neurodegeneration. However, the precise roles and mechanism(s) of action of Tβ4 in these processes remain 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 part 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 iron$^{2+}$and iron$^{3+}$ binding regions along the peptide and show that the presence of Tβ4 in cell growing medium inhibits erastin and glutamate-induced ferroptosis in macrophage cell line. Moreover, Tβ4 increases the expression of oxidative stress-related genes, namely BAX, hem oxygenase-1, Heat shock protein 70 and Thioredoxin reductase 1, which are downregulated during ferroptosis. We state the hypothesis that Tβ4 is an endogenous iron chelator and take part of iron homeostasis in 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 shows that controlled Tβ4 release could command on/off switching of ferroptosis, and may provide novel therapeutic opportunities in pathologies of cancer and tissue degeneration.
dc.description.sponsorshipFinancial support from FIR 2019 and from Regione Autonoma della Sardegna (grant RASSR79857) is gratefully acknowledged. We acknowledge the CeSAR (Centro Servizi d'Ateneo per la Ricerca) of the University of Cagliari, Italy for the Transmission Electron microscopic analysis performed with the JEOL 1400 plus TEM.
dc.publisherResearch Square Platform LLC
dc.relation.urlhttps://www.researchsquare.com/article/rs-677051/v1
dc.relation.urlhttps://www.researchsquare.com/article/rs-677051/v1.pdf?c=1625886701000
dc.rightsArchived with thanks to Research Square Platform LLC
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectThymosin β4
dc.subjectanti-inflammatory
dc.subjectneurodegeneration
dc.subjectmacrophage cell
dc.subjecttissue degeneration
dc.titleThymosin β4 is an Endogenous Iron Chelator and Molecular Switcher of Ferroptosis
dc.typePreprint
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.contributor.departmentBioscience
dc.contributor.departmentBioscience Program
dc.contributor.departmentNMR
dc.eprint.versionPre-print
dc.contributor.institutionUniversity of Cagliari, Cittadella Universitaria
dc.contributor.institutionUniversity of Cagliari
dc.contributor.institutionKimika Fakultatea, Euskal Herriko Unibertsitatea UPV/EHU, Donostia International Physics Center (DIPC)
dc.contributor.institutionNational Research Council (Consiglio Nazionale delle Ricerche)
dc.contributor.institutionUniversity of Erlangen-Nuremberg
kaust.personChandra, Kousik
kaust.personSzczepski, Kacper
kaust.personJaremko, Lukasz
kaust.personGhosh, Mitra
kaust.personEmwas, Abdul-Hamid M.
kaust.personJaremko, Mariusz
refterms.dateFOA2021-07-12T06:13:31Z


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