Effect of Pimecrolimus on apoptotic pathways in H2O2-treated neuron like differentiated-SH-SY5Y cells: a molecular docking and mechanistic study

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dc.authorid0000-0002-7248-7933
dc.contributor.authorKocanci, Fatma Gonca
dc.date.accessioned2026-01-24T12:29:00Z
dc.date.available2026-01-24T12:29:00Z
dc.date.issued2025
dc.departmentAlanya Alaaddin Keykubat Üniversitesi
dc.description.abstractNeurodegenerative diseases (NDs), including Alzheimer's and Parkinson's, are marked by progressive neuronal loss, driven largely by oxidative stress and apoptosis. Developing neuroprotective strategies to counteract these processes is critical for managing such disorders. This study explores the neuroprotective effects of pimecrolimus, a calcineurin inhibitor, in mitigating hydrogen peroxide (H2O2)-induced cytotoxicity in neuron-like differentiated SH-SY5Y (d-SH-SY5Y) cells. The investigation focuses on apoptosis modulation, cell viability, and molecular docking interactions with apoptotic proteins.SH-SY5Y cells were differentiated with retinoic acid and treated with H2O2 (250 mu M) alone or in combination with pimecrolimus (0.01, 0.1, and 1 mu M) for 24 h. Cell viability was assessed using lactate dehydrogenase (LDH) assays. Additionally, malondialdehyde (MDA) levels were measured to assess oxidative stress in SH-SY5Y cells following the treatment conditions. Molecular docking analyses evaluated pimecrolimus' interactions with bax, bcl-2, caspase-3 and caspase-8 proteins, using Venetoclax as a positive control. Apoptosis-related protein levels were analyzed via ELISA, qRT-PCR, and immunofluorescence staining (cleaved caspase-3 and DAPI).Molecular docking showed strong binding of pimecrolimus to bax, bcl-2, caspase-3 and caspase-8, with comparable binding energies to Venetoclax. LDH and MDA assays demonstrated significant reductions in H2O2-induced cytotoxicity with pimecrolimus. ELISA and qRT-PCR revealed that H2O2 increased pro-apoptotic bax, caspase-3 and caspase-8 levels while decreasing anti-apoptotic bcl-2 levels. Pimecrolimus co-treatment reversed these effects in a dose-dependent manner. Immunofluorescence confirmed reduced apoptosis and cell death with pimecrolimus.Pimecrolimus effectively mitigates oxidative stress and apoptosis in H2O2-treated d-SH-SY5Y cells. These findings suggest its potential as a neuroprotective agent for managing (NDs).
dc.identifier.doi10.1093/toxres/tfaf020
dc.identifier.issn2045-452X
dc.identifier.issn2045-4538
dc.identifier.issue1
dc.identifier.pmid39968517
dc.identifier.scopus2-s2.0-85219497833
dc.identifier.scopusqualityQ3
dc.identifier.urihttps://doi.org/10.1093/toxres/tfaf020
dc.identifier.urihttps://hdl.handle.net/20.500.12868/5041
dc.identifier.volume14
dc.identifier.wosWOS:001422283100001
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherOxford Univ Press
dc.relation.ispartofToxicology Research
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WoS_20260121
dc.subjectneuroprotection
dc.subjectoxidative stress
dc.subjectapoptotic pathways
dc.subjectpimecrolimus
dc.subjectSH-SY5Y cells
dc.titleEffect of Pimecrolimus on apoptotic pathways in H2O2-treated neuron like differentiated-SH-SY5Y cells: a molecular docking and mechanistic study
dc.typeArticle

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