A new underlying mechanism for the neuroprotective effect of bosutinib: Reverting toxicity-induced PARylation in SIN1-mediated neurotoxicity

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dc.contributor.authorYilmaz, Sinem
dc.contributor.authorAlkan, Tolgaç
dc.contributor.authorBallar Kirmizibayrak, Petek
dc.date.accessioned2026-01-24T12:20:45Z
dc.date.available2026-01-24T12:20:45Z
dc.date.issued2021
dc.departmentAlanya Alaaddin Keykubat Üniversitesi
dc.description.abstractIncreased levels of reactive oxygen and nitrogen species play an important role in the development and progression of neurodegenerative diseases, such as Alzheimer's and Parkinson's disease. The overproduction of these highly reactive chemical species leads to DNA damage and subsequent activation of the poly(ADP-ribose)polymerase (PARP) enzyme. Several studies have demonstrated the potential use of PARP inhibitors for neuroprotection. We previously reported that the dual Src/Abl kinase inhibitor bosutinib (BOS) decreases PARP activity and acts as a chemosensitizer in cancer cells. In this study, we evaluated the neuroprotective potential of BOS with respect to its inhibitory effect on cellular poly(ADP-ribos)ylation (PARylation) using a 3-morpholinosydnonimine (SIN1)-mediated cellular toxicity model. Our data suggest that pretreatment with BOS, especially at lower doses, significantly decreased the level of SIN1-induced cellular PARylation. This regulation pattern of PARylation was found to be associated with the protective effect of BOS against SIN1 on the viability of retinoic acid-differentiated SH-SY5Y cells. Furthermore, while PARP-1 expression was decreased, phosphorylation of SAPK/JNK was not reverted at the observed neuroprotective doses of BOS. In conclusion, we suggest a novel mechanism for the neuroprotective effect of BOS involving the inhibition of cellular PARylation. © 2021 Wiley Periodicals LLC
dc.description.sponsorship(2209?A); Ege Üniversitesi; Türkiye Bilimsel ve Teknolojik Araştirma Kurumu, TÜBITAK
dc.identifier.doi10.1002/jbt.22915
dc.identifier.issn1095-6670
dc.identifier.issue12
dc.identifier.pmid34519134
dc.identifier.scopus2-s2.0-85114791221
dc.identifier.scopusqualityQ2
dc.identifier.urihttps://doi.org/10.1002/jbt.22915
dc.identifier.urihttps://hdl.handle.net/20.500.12868/4561
dc.identifier.volume35
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherJohn Wiley and Sons Inc
dc.relation.ispartofJournal of Biochemical and Molecular Toxicology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_Scopus_20260121
dc.subjectbosutinib
dc.subjecthuman neuroblastoma cells
dc.subjectneuroprotection
dc.subjectPARylation
dc.subjectSIN1 (3-morpholinosydnonimine)
dc.titleA new underlying mechanism for the neuroprotective effect of bosutinib: Reverting toxicity-induced PARylation in SIN1-mediated neurotoxicity
dc.typeArticle

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